Pacemaker with improved automatic output regulation

ABSTRACT

A pacemaker which is provided with an improved automatic regulation circuit which is capable of distinguishing between a fashion beat and loss of capture. The failure to sense an evoked potential following a stimulus may be due to either. The cause is determined by generating a high-energy back-up pulse shortly after the stimulus. Failure to capture by the back-up pulse is an indication that there was just a fusion beat; the sensing of an evoked potential is an indication that the stimulus failed to capture.

This is a division of application Ser. No. 173,566 filed Mar. 25, 1988,now U.S. Pat. No. 4,878,497.

This invention relates to pacemakers, and more particularly topacemakers with automatic output regulation.

Automatic output regulation (control of output energy) in a pacemaker, atype of self-adaptation, involves testing for the lowest possible pulseoutput energy which results in heart capture, a concept not unknown inpacing but one which has not achieved high grades for successfulimplementation. What often confounds an automatic output regulationcircuit is a fusion beat. A fusion beat is a combined intrinsic andpaced event; the pacemaker does not have enough time between start ofthe intrinsic beat and timeout of the escape interval to inhibitgeneration of a stimulus. A fusion beat is difficult to sense and canlead to an erroneous determination that there has been a loss of captureand that there is therefore a need to increase the output pulse energy.

It is an object of our invention to provide an improved automatic outputregulation scheme for an implantable pacemaker, one which is capable ofdistinguishing between fusion beats and loss of capture.

In the event of an apparent loss of capture, in the illustrativeembodiment of the invention, the pacing rate is increased slightly toavoid fusion beats if that is really the problem. Furthermore, a back-uppulse (of high energy) is generated shortly after the failure to sensean evoked response from the preceding ordinary stimulus. If the back-uppulse fails to evoke a response, it is an indication that the precedingstimulus resulted in a fusion beat. Only if the back-up pulse gives riseto an evoked potential is it made clear that the preceding stimulusresulted in a heart capture failure and that the output pulse energy mayhave to be increased.

Further objects, features and advantages of our invention will becomeapparent upon consideration of the following detailed description inconjunction with the drawing, in which:

FIG. 1 depicts a pacemaker with a standard bipolar lead;

FIG. 2 is a timing diagram which shows the relationships among certainevents which take place during a single cardiac cycle;

FIG. 3 is a schematic block diagram of a single-chamber pacemakerconstructed in accordance with the principles of the present invention;

FIG. 4 is a schematic block diagram of the charge dump circuit used inthe pacemaker of FIG. 3;

FIG. 5 depicts a sensed evoked potential as a function of time;

FIG. 6 depicts the depolarization gradient (integrated value) of theevoked potential of FIG. 5;

FIG. 7 is a more complete representation of the illustrative embodimentof the invention;

FIG. 8 depicts the manner in which the depolarization gradient (RCP)changes with stress;

FIG. 9 depicts the manner in which the depolarization gradient (RCP)changes with packing rate;

FIG. 10 depicts the manner in which the depolarization gradient (RCP) ismaintained constant in a closed-loop control system;

FIG. 11 is a table which shows the way in which output energy is changedduring automatic output regulation;

FIGS. 12 and 13 depict two examples of the way in which the table ofFIG. 11 is used;

FIGS. 14-17 are timing diagrams which depict several different modes ofoperation of the pacemaker of our invention;

FIG. 18 depicts symbolically the way in which the value of target isadjusted in the illustrative embodiment of our invention;

FIGS. 19-28 comprise a low-level flow chart which depicts themethodology of the pacemaker operation; and

FIGS. 29 and 30 are high-level flow charts of the threshold search andtarget initialization procedures.

ILLUSTRATIVE EMBODIMENT--RATE-RESPONSIVE PACEMAKER

In order to describe our automatic output regulation system, someillustrative pacemaker must be chosen as the vehicle for disclosure. Wechoose a rate-responsive pacemaker, one which has great advantages overthose of the prior art.

In order to satisfy the metabolic needs of a patient, it is advantageousto implant a rate-responsive pacemaker. Such a device responds to somerate control parameter (RCP) which is indicative of the body's need forcardiac output. The measured value of the rate control parameter("MRCP") is used to adjust the pacing rate. In the copending applicationof Frank Callaghan entitle "Rate Responsive Pacing Using the Magnitudeof the Depolarization Gradient of the Ventricular Gradient," Ser. No.810,877 filed on Dec. 18, 1985, which application is hereby incorporatedby reference, there are described numerous rate control parameters whichmay be used. The particular parameter which is the focus of thatapplication is the depolarization gradient--the integral of the QRSsegment of an evoked potential. The magnitude of the depolarizationgradient has been found to be an excellent indicator of cardiac outputneeds.

One of the most formidable problems in designing a rate-responsivepacemaker is to devise an algorithm which relates the MRCP to pacingrate--even assuming that the MRCP is measured correctly. It would behighly advantageous to provide a closed-loop control system for arate-responsive pacemaker. Such a negative feedback system would allowthe control of pacing rate automatically. Instead of having to derive orlook up in a table the value of pacing rate which is to be set for eachMRCP, a closed-loop control system would simply change the rate in thedirection which tends to keep the MRCP constant. If the MRCP tends tochange in either direction, the rate adjusts in a direction whichreturns the MRCP to its value before the change.

What makes the depolarization gradient an excellent rate-controlparameter is that increased stress (including both emotional stress andexercise) causes the depolarization gradient to decrease while anincreased heart rate causes the depolarization gradient to increase. Itis the opposite effects which stress and heart rate have on thedepolarization gradient that permits a closed-loop control system to beeffected. An increase in stress causes the MRCP to decrease. In the caseof increased stress, what is desired is an increased rate. Thus thepacemaker is made to respond to a decrease in MRCP by increasing itsrate. But when the rate increases, do does the MRCP; the MRCP increaseis in a direction which is opposite to the original MRCP decrease. Whenthe increase in MRCP due to faster pacing cancels the original decrease,the pacing rate stops increasing. The governing rule is that when thereis a change in MRCP, the rate is changed so that MRCP moves in theopposite direction, until MRCP is restored. This is a negative feedbacksystem, and it avoids the need for a complex relationship between ameasurement value and the way in which the pacing rate should change.

Reference is made to an article entitled "Central Venous OxygenSaturation for the Control of Automatic Rate-Responsive Pacing,"Wirtzfeld et al, PACE, Vol. 5, Page 829, November-December 1982. Thethesis of this article is that central venous oxygen saturationrepresents the only rate-control parameter which is suitable for therealization of a closed feedback loop. The thesis is incorrect becausethe depolarization gradient is another parameter which allowsclosed-loop control. One of the major advantages which thedepolarization gradient has over central venous oxygen saturation isthat an additional sensor is not required. The cardiac signal whichappears on the pacemaker lead can be processed such that thedepolarization gradient is determined without requiring the provision ofan additional sensor.

Unfortunately, simply selecting a rate-control parameter whichtheoretically lends itself to closed-loop control is not enough. Theobject of a closed-loop control system is to maintain a controlparameter constant. In the case of a rate-responsive pacemaker, it wouldappear that it is the MRCP which must remain constant; any change inMRCP caused by stress controls a change in rate which returns the MRCPto the desired (constant) value. (A particular MRCP is suitable, ofcourse, only if maintaining the MRCP constant indeed provides thedesired pacing rates for all metabolic needs to be handled). The problemis that rate control parameters change not only with stress, but alsodue to other factors. The most important of these is perhaps drugs. Manyrate control parameters are affected by the taking of drugs. Thus if anMRCP increases due to the patient having taken a drug, and no change hasotherwise taken place in this metabolic needs, it is not desirable forthe pacing rate to change in such a way that the MRCP will be returnedto its previous value. Furthermore, the operation of a mechanical orchemical sensor may change with time. Even when measuring thedepolarization gradient and using it as a rate-control parameter, if forone reason or another the lead shifts in position it is possible for ashift to appear in the MRCP. In such a case, without some way tocompensate for a non-stress change in MRCP, a closed-loop control systemwould effect a permanent shift in pacing rate. The Wirtzfeld et alclosed-loop control system did not provide compensation for this type ofshift in the rate-control parameter; as far as we know, the Wirtzfeld etal pacemaker has not been commercialized. It is anything but a simplematter to compensate for drifts in a rate-control parameter which areunrelated to stress.

In the illustrative embodiment of our invention, the pacing rate is notchanged in a direction which tends to keep MRCP constant. Instead, thepacing rate is adjusted in accordance with a parameter denominated as(MRCP-target), where target is a value indicative of changes in MRCP dueto non-stress and non-rate factors (such as changes which result fromlead maturation, drugs, etc.). Exactly how the value of target isderived requires careful analysis, although once the concept is graspedit will be seen that there are only three simple rules which must beemployed. How target is derived will be described in detail below.

In the illustrative embodiment of the invention, the depolarizationgradient is the integral of the QRS waveform of an evoked potential. Notevery QRS waveform must be processed, but QRS waveforms must beintegrated often enough to allow MRCP up-dating to follow metabolicchanges. Since it is evoked potentials which are measured in theillustrative embodiment of the invention, this means that periodicallystimulated beats must take place, as opposed to intrinsic beats. Someway must be found to pace the heart periodically even if pacing pulsesare not otherwise required. This is accomplished by increasing thepacing rate on an individual beat basis to just above the intrinsic ratewhen an MRCP sample is required.

Because the heart is paced in the illustrative embodiment of theinvention approximately every fourth beat in order that an MRCP sampleis taken, it is especially important to use the lowest possible energyin each pulse in order to extend battery life and to minimize distortionof MRCP due to lead polarization. It is therefore particularly importantto provide improved automatic output regulation.

DESCRIPTION OF HARDWARE

The single-chamber cardiac pacing system 10 of FIG. 1 includes a pulsegenerator 12 which is of generally conventional design except asotherwise described herein. Bipolar lead 14 also is of conventionaldesign. For example, tip electrode 16 may be a porous, platinum-iridium,hemispherically-shaped electrode on the distal end of lead 14. Ringelectrode 18 is typically spaced at least 0.5 cm from tip electrode 16.

The circuitry of pulse generator 12 is sealed in a hermetic container,for example, titanium can 20, as shown. When the pacer can 20 is treatedas an independent electrode, the single-chamber cardiac pacing system 10carries three electrodes: can 20, tip electrode 16 and ring electrode18. The operation of the pacing system as described can apply to theventricular lead of a dual-chamber cardiac pacer. However, for purposesof simplicity of disclosure, the details of operation will be disclosedfor only a ventricular pacer.

A pacing cycle begins when an electrical stimulus is emitted from tipelectrode 16 to stimulate muscular contraction of at least a portion ofthe heart. The stimulus is of a magnitude and width which is not harmfulto the heart and which is well known to those skilled in the art toevoke a contraction response from the heart muscle. The pulse ofelectric stimulus 30 is graphed in FIG. 2 as signal A, having a typicalduration of 0.1 to 2 milliseconds.

Referring to the circuit of FIG. 3, pacer can 20 is shown serving as areference electrode for electrodes 16 and 18. Stimulus 30 is transmittedvia conductor 22 to tip electrode 16. The naturally occurring cardiacelectrical activity is amplified by sense amplifier 44 and transmittedvia line 31 to a spontaneous event and noise detector 46 to begin atiming process. The signal is extended via conductor 26 into timing andcontrol circuitry module 50 which, in turn, has feedback and controllines 28, 29 connected, respectively, to detector 46 and to evokedresponse detector 54. Likewise, an output from timing and controlcircuit 50 is connected via line 35 to output and charge dump circuit48. In the presence of noise, spontaneous event and noise detector 46extends a corresponding control signal on conductor 27 to the timing andcontrol circuit 50.

Immediately following the emission of pulse 30 from electrode 16, chargedump circuit 48 is activated, with the charge dump pulse 34 beingillustrated as signal B of FIG. 2, the duration of the charge dump beingabout 5 to 15 milliseconds. The charge dump may be provided using aconventional charge dump circuit 48 such as illustrated in FIG. 4.During the charge dump period, the electrical charge on output couplingcapacitor 60 (FIG. 4) and tip electrode 16 are discharged through theheart 21. Thus the post-stimulus polarization potential of electrode 16is quickly diminished.

Evoked response detector 54 is then activated by timing and controlcircuit 50 over conductor 29. A window of time 36 is opened asillustrated by signal C of FIG. 2, its magnitude being typically 60milliseconds. It is only during this time that evoked response detector54 is activated to detect an evoked electrical response from the heart.

The stimulus from electrode 16 can be seen to be in the unipolar mode.Likewise, detection of the evoked response is unipolar, being detectedby ring electrode 18, which communicates over conductor 72 and throughamplifier 52 to detector 54. Detector 54 transmits the detected signalvia line 55 to integration circuit 57. The integrated signal, which isdiscussed in detail below, is transmitted to timing and control circuit50 via line 59.

It is noted that the window of time 36 shown as signal C in FIG. 2 ispositioned in a block of time 32 (signal D of FIG. 2) which generallyrepresents a refractory period. However, the evoked response can bedetected during a refractory period 32.

Signal E in FIG. 2 shows the evoked cardiac electrical activity 38within evoked response detection period 36, and which is detected byring electrode 18. The evoked heartbeat response 38 is detected by ringelectrode 18 in the unipolar mode. The detected evoked response is fedvia line 55 to integration circuit 57, and the output of the integrationcircuit is extended via line 59 to timing and control circuit 50.

However, there is a need to detect natural heartbeats to avoid theresult of the pacing system disrupting and interfering with the naturalheartbeats. To this end, beginning essentially at the end of refractoryperiod 32, during which spontaneous event detector 46 is disabled fromsensing cardiac signals, an alert period 40 (signal F; FIG. 2) isprovided to monitor naturally occurring cardiac electrical activityuntil such time as the next pulse 30 is applied to tip electrode 16.

Detector circuitry 46 may be activated and shut down by timing andcontrol circuit 50 via line 28. During the alert period 40, bothelectrodes 16 and 18 operate together in a bipolar configuration, withboth electrodes communicating with amplifier 44, which in turn isconnected to spontaneous event detector 46. (If desired, intrinsic beatscan be sensed using a unipolar configuration.)

In the event of a spontaneous heartbeat, a signal may be sent fromspontaneous event detector 46 via line 26 to timing and control circuit50, to cause the electronics to recycle from any time in the cycle tothe beginning of the cycle, without generation of an electric pulse 30from tip electrode 16. Every time natural cardiac electrical activitytakes place during alert period 40, no stimulus will be generated.

In the event, however, that detector 46 does not detect natural cardiacelectrical activity during the alert period, timing and control circuit50 will cause another pulse to be generated via electrode 16.

Referring to FIG. 5, a typical cardiograph tracing of the changingpotential in the ventricle of a heart is shown throughout most of asingle cardiac cycle with respect to a reference base line ofpredetermined voltage, typically zero volts. For purposes of thisinvention, the Q-point represents the beginning of the R-wave 152 wherethe voltage trace crosses or is closest to the base line 154, prior toforming R-wave 152. The R-point is the peak of R-wave 152, irrespectiveof whether the trace is shown in its form of FIG. 5 or in inverted form,which is possible with other recording systems. The S-point is where thetrace crosses base line 154.

In operation, as illustrated in FIG. 3, the evoked potential is detectedon ring electrode 18. The signal is transmitted via heart amplifier 52and detector 54 to integration circuit 57 via line 55. The integratedsignal 140 is known as the depolarization gradient, and is illustratedin FIG. 6. Referring to FIG. 6, the major parameter of interest to thepresent invention is the magnitude 162 of the depolarization gradient140, from the base line 154 to the peak 148.

During periods of heart stress, the area of R-wave 152 decreases inmagnitude. Therefore, the depolarization gradient will similarlydecrease in magnitude. The depolarization gradient lends itself todetection and analysis. The occurrence of bimodal R waves will notnegatively impact upon the value of the depolarization gradient as astress measuring tool.

The depolarization gradient is calculated and compared to a targetvalue. If the depolarization gradient is equal to the target value,there is no change in the heart pacing stimulus rate. The escapeinterval remains the same. If the depolarization gradient is smallerthan the target value, a determination is made as to whether or not thestimulus rate is at its programmed maximum rate. If it is at its maximumrate, the stimulus rate is not increased. However, if the stimulus rateis less than the programmed maximum rate, the rate is incremented bysome predetermined value. Should the depolarization gradient increase,indicating a reduction in stress, the determination is made as towhether or not the rate of stimulation is at its minimum programmedrate. If it is at the programmed minimum rate, there is no furtherdecrease in rate. If it is not at its minimum programmed rate, the rateof the stimulation is decreased by some predetermined value.

Spontaneous electrical events such as those conducted from the atrium tothe ventricle via the cardiac conduction pathway or those arising withinthe ventricle itself (premature ventricular contractions) are detected.These signals are amplified by the amplifier 44 and detected in thespontaneous event and noise detector 46. The timing and control circuit50 acts upon these events to reset the escape interval. (Further, thesespontaneous electrical events may be integrated if desired, and thedepolarization gradient may be determined. Rate changes or escapeinterval changes may be implemented based on the depolarization gradientof the spontaneous electrical events in the same manner that they areimplemented based on the depolarization gradient of the evokedpotentials. To this end, the integration circuit 57 of FIG. 3 is shownas receiving the signal from spontaneous event and noise detector 46 vialine 160, although only evoked potentials are processed in theillustrative embodiment of the invention.)

A relatively detailed schematic diagram of the pacer electronics ispresented as FIG. 7. Referring to FIG. 7, it is seen that the samereference numerals are used for the same components of FIG. 3. Timingand control circuit 50 comprises a microcomputer 190 which addresses amemory 192 via address bus 194. Data bus 196 is coupled betweenmicrocomputer 190 and memory 192, and conventional control logic 198 iscoupled to data bus 196. A crystal controlled clock 200 is used forproviding appropriate clock pulses for the system. The functions of thecontrol logic inputs and outputs are designated. The drawing of FIG. 7also shows a programming/telemetry transceiver 220 for allowingsupervisory information and data to be telemetered out for reception bya programmer or other receiving device, and for allowing the pacemakerto be programmed by an external programmer, as is well known in the art.

Control logic circuit 198 provides a gradient measure enable signal toelectronic switch 202 and to analog-to-digital converter 204 which is atthe output of an integrating amplifier 206. It can be seen that theamplified potential sensed at ring 18 is applied to the negative in putof the integrating amplifier 206 which, when enabled, provides anamplified analog output that is converted to digital data by means ofanalog-to-digital converter 204. The digital data contains thedepolarization gradient information, which is provided to the controllogic circuit 198 whereby appropriate timing of the stimulation pulsesis achieved in response thereto.

The gradient measure enable signal 210 is illustrated as signal G onFIG. 2. It commences at the same time that the capture detection window36 commences and the gradient measure enable signal 210 continues for upto 130 milliseconds. The several control signals depicted on FIG. 7 arefor the most part self-explanatory. For example, it will be apparentthat spontaneous event and noise detector 46 is provided with aprogrammable reference voltage which serves as a threshold. It isenabled to sense R waves by an alert period window signal. The twosignals which it provides to the control logic represent the sensing ofan intrinsic beat or the presence of noise.

THE DEPOLARIZATION GRADIENT AS A RATE-CONTROL PARAMETER

The reason that the depolarization gradient lends itself to closed-loopcontrol is exemplified by FIGS. 8, 9 and 10. The key to the closed-loopcontrol is that the physiological effects of emotional or physicalstress cause the RCP to become smaller, whereas increased heart ratecauses the RCP to become larger.

The opposite effects of stress and heart rate on the depolarizationgradient are shown in FIGS. 8 and 9, in which the RCP refers to thedepolarization gradient. The bottom of the first graph shows the patientat rest, then starting to exercise, then exercising more strenuously,and finally returning to rest. This is referred to as the workload. Thepatient's heart is paced at a fixed rate in the case illustrated in FIG.8, at a rate of 70 pulses per minute. The top of the graph shows theRCP, measured in microvolt-seconds, as decreasing with increasingstress. Thus FIG. 9 shows how the RCP decreases if the heart rate doesnot increases when the patient is under stress. In contrast, the graphof FIG. 9 shows what happens if the heart rate is increased to a valuehigher than that required for the current state of stress; in such acase the RCP increases. As seen in FIG. 9, the patient is at rest butthe heart rate is arbitrarily increased and then decreased over a periodof 5 minutes. The RCP is seen to increase with increasing rate. TogetherFIGS. 8 and 9 show that increased stress and increased heart rate haveopposite effects on the RCP.

It is this phenomenon that allows a stabilizing feedback mechanism to beestablished. The graph of FIG. 10 depicts the rate response of theclosed-loop control mechanism of our invention. As stress increases (anincrease in exercise), the RCP tends to decrease (FIG. 8); however, anytendency for the RCP to decrease causes the control mechanism toincrease the heart rate. The increase in heart rate restores the RCP toits pre-change value (FIG. 9). The net result of maintaining the valueof RCP constant is that the heart rate follows the patient's workload.This is the significance of what is shown in FIG. 10: simply bymaintaining the RCP constant, the heart rate can be made to follow themetabolic needs of the patient without any complicated relationshipbetween RCP and heart rate having to be devised.

THE RATE-RESPONSE ALGORITHM

The basic rule is that when there is a change in the measured value ofthe RCP (MRCP), the rate should be increased or decreased in thedirection which restores MRCP. But while the basic rule is simple tostate, it is not sufficient to implement a closed-loop control system.The reason is due to changes which occur over long periods of time (longcompared to how fast MRCP changes due to stress) because of otherfactors, e.g., drugs. If a drug causes MRCP to decrease and to remainlower than it otherwise would be, then the pacer will cause the pacingrate to be higher than it should be; the pacer does not know why MRCPdecreased and would blindly follow the rule to increase the rate so thatMRCP remains constant. Simple control of the type described does notwork in the absence of compensation for changes in MRCP due to factorsother than those related to stress.

The solution is to control rate in a feedback network not so that MRCPstays constant, but so that (MRCP-target) stays constant. Target is avalue which ideally changes with non-stress "inputs"; it changes thesame way as those "inputs" affect MRCP. Drugs may change MRCP, but ifthey also change target by the same amount, the controlparameter--(MRCP-target)--affects rate in accordance with only changesin MRCP due to stress. The operative rule is to change rate in adirection which compensates for changes in (MRCP-target), with targetremaining constant over the short term and thus allowing the pacer torespond to stress changes.

Now if (MRCP-target) decreases, for example, it is assumed that it isdecreasing because MRCP decreased in response to the patient starting toexercise. The MRCP still changes in accordance with stress and rate inopposite directions (which is why the control system works in the firstplace). The MRCP also still changes in accordance with other "inputs",but now the effect of these other inputs on the control loop iscancelled by having target respond to these inputs in the same way thatMRCP does, and by using (MRCP-target) as the control parameter. Thecontrol system is not only closed-loop, but adaptive as well.

The question is how to get target to reflect changes in MRCP which aredue to non-stress factors, i.e., how to get the pacer to self-adapt. Wewill give some rules to follow, and then see why they work.

What is desired is that the pacer pace at or near the minimum rate inthe absence of exercise, i.e., most of the time the minimum rate iswanted. Whenever the rate is above the minimum rate (due to rateresponse taking place), the pacer imposes a very small bias which slowlyreturns the rate to the minimum by decreasing target; this is done justin case the reduced MRCP which is causing pacing above the minimum rateis really due to drift. The bias is so small that the tendency todecrease the rate is overpowered by changes in the rate-response systemdue to stress (increased or decreased rate). Eventually a return is madeto minimum rate. The usual reason is that the patient has stoppedexercising. But if there was a drift and the rate could not be returnedall the way by the control system, a full return will still occurbecause of the slowly decreasing target value. As (MRCP-target) thusslowly increases, the rate slowly decreases as desired, all the way downto minimum rate. Thus Rule 1, applicable during rate-responsive pacing,is to decrease target slightly during each MRCP measurement cycle, ifthe present rate is above the minimum rate. Changing target this way isin addition to changing the rate in accordance with the new value of(MRCP-target).

Consider now a positive value of (MRCP-target) when minimum rate isreached. Pacing is at the minimum rate and is not going any lower. MRCPmay have changed due to drift, but the present MRCP is what is now beingmeasured for minimum rate. No more changes in rate are desired (in theabsence of stress changes); the rate is where it should be. At theminimum rate, (MRCP-target) should equal zero. The reason is that shouldstress increase, i.e., the patient start to exercise, it is desired that(MRCP-target) go negative so it can control a rate increase. If targetis too small and (MRCP-target) is positive, (MRCP-target) may not gonegative when MRCP decreases. Before it could become negative andcontrol a rate increase, MRCP would have to decrease appreciably just toget rid of the unnecessary positive residue (introduced by forcingtarget down during rate-response pacing, and possibly drift). To avoidthis kind of lag, when pacing is at the minimum rate (MRCP-target) ismade equal to zero by increasing target as much as necessary--until itequals MRCP. When exercise then starts, the slightest decrease in MRCPdue to stress will make (MRCP-target) negative, and the rate will startincreasing. So Rule 2 is to increase target until it equals MRCPwhenever minimum rate is achieved. Moreover, target is increased veryrapidly so that the pacemaker will be ready to increase the pacing rateas soon as exercise commences.

When minimum rate is achieved, (MRCP-target) cannot be negative. Anegative value for (MRCP-target) causes the rate-response system tocontrol a rate increase, i.e., above minimum rate; thus (MRCP-target)cannot be negative at minimum rate. If (MRCP-target) is zero at minimumrate, there is nothing to do; there is equality between MRCP and target,rate response leaves the rate as is, and it is just where it is desired.In fact, when (MRCP-target) is positive, target is increased preciselyso that a difference of zero is obtained. When the pacing rate is aboveminimum rate due to rate response, on the other hand, target is reducedcontinuously, albeit slowly. As target is decreased, so is rate. Whathappens is that eventually (MRCP-target) is positive when minimum rateis obtained--either because target has been decreased by the built-inbias, or, more commonly, the patient has stopped exercising. It is asthis time that target is rapidly increased until it equals MRCP.

The original question was how to derive a value for target whichreflects changes in MRCP which are due to non-stress factors. Thequestion has been answered by the two Rules just given. The pacer maynot know that the non-stress factors have done to MRCP. But it does knowthat the feedback loop, controlled by (MRCP-target), is controlledpacing at the minimum rate. The pacer may be measuring a different valueof MRCP than it did yesterday for the same conditions, but whatever thenew value, target is just right for it to give the minimum rate for thisparticular value of MRCP. And once the correct value of target is hadfor one rate, it can be used for all rates; target stays constant overthe short term. When minimum rate is reached, target may be too small[(MRCP-target) is positive] and must be increased because the built-inbias made it too small by continuously reducing it while rate responsewas operative. Whenever a return is made to minimum rate, as alwayshappens, the pacer adjusts target to correct for what it did to it andalso for non-stress inputs which have occurred since the last time adeparture was made from minimum rate.

How fast target must be decreased (whenever the current rate is aboveminimum) depends on the patient. If he will exercise for long periods oftime, then since target is continuously decreased the pacing rate mayeventually return to minimum rate even though he is still exercising. Sofor such a patient, target should be decreased very slowly. For thepatient who takes drugs every two hours and whose MRCP keeps changingrapidly (due to things other than stress), calibration should be muchfaster. An advantage of the design is built-in safety. No one, not evenan exercising patient, should be paced at high rates forever. Even hisslow calibration speed eventually causes target to decrease enough tolower the rate. But the slow calibration speed lets him exercise forlengthy periods of time before the automatic reducing of targeteventually has much of an effect on reducing the rate. As will bedescribed, three calibration speeds during rate-response pacing can beprogrammed.

Suppose a patient exercises for a long time, until target has beenreached appreciably. When he stops, MRCP increases. Now (MRCP-target) ismuch greater than it otherwise would be because target was reduced as aresult of the built-in bias (Rule 1, applicable during rate response).The rate now drops down, usually all the way to the limit of the minimumrate. If the patient starts exercising again, (MRCP-target) would stillbe high due to the low value of target, and rate response would keeprate low even though a higher rate is wanted. That is why, a minimumrate, target is increased very rapidly. In just a few minutes, targetrises to MRCP. When exercise then resumes and MRCP drops, target is highenough to allow a high rate to be controlled. Calibration is orders ofmagnitude faster when target is being increased at minimum rate than itis when the rate is above minimum rate and target is being decreased.(Actual calibration speeds will be discussed below.)

The decrease in target during rate-response pacing is designed to forcea return to minimum rate at which time target can be corrected. Usually,minimum rate will be achieved because the patient stops exercising atwhich time target is corrected to compensate for non-stress effects onMRCP. Decreasing target during rate-response pacing to force a return tominimum rate is the pacer's fail-safe mechanism.

This far two cases have been considered: (1) pacing above minimum rate[target is decreased at one of three calibration speeds], and (2) pacingat minimum rate [only if (MRCP-target) is positive is target increased,very rapidly]. But there is a third case--an intrinsic rhythm fasterthan the minimum rate. As will be described below, on every fourth beatoverdriving (pacing at a rate faster than the intrinsic rate) iscommenced until an evoked response is obtained so that MRCP can bemeasured. The question is what is done to target in this third case.

An intrinsic rhythm is really a minimum rate; it is higher than theprogrammed value, but the intrinsic rate will not permit the pacer topace more slowly. So it is treated like case 2, with on difference:target is increased as in case 2, but at the programmed calibrationspeed used for case 1 (not the very fast speed of case 2). This is Rule3. The reason is that the intrinsic rate may be due to some pathologicalfactor. When target is increased, in effect the pacer is controlled topace at a higher rate. If target is rapidly increased, as in case 2, allrates would be biased upward just because momentarily there was apathologically high intrinsic rate. To avoid this, target is increasedslowly when the intrinsic rate is higher than the minimum rate (case 3),just as it is slowly decreased in case 1.

It should be noted that as target increases in case 3, (MRCP-target)decreases and rate increases. Eventually the rate-response system maycause the rate to increase above the intrinsic rate and pacingbegins--case 1. Now target starts decreasing (case 1), the ratedecreases, and eventually the rate falls below the intrinsic rate andcase 3 is obtained again. The modes may alternate: for one period oftime there is an intrinsic rhythm, then a number of paced beats justslightly faster, than an intrinsic rhythm, etc. Note that as soon as thepatient starts to exercise, (MRCP-target) decreases and rate responsecauses the rate to increase starting just above the intrinsicrhythm--just what is wanted when exercise begins. Also, if the patient'sheart stops beating spontaneously, pacing commences near the previousintrinsic rate even though it is higher than the minimum rate.

Alternations of the type described (case 1, case 3) can be avoided(although it is not even necessary to do this). When in mode 3, insteadof increasing target every time an MRCP measurement is made, it shouldnot be increased if (MRCP-target) is less than some small limit. Thiswill keep the pacer operating in mode 3 (unless there is a drift, inwhich case it is desired that target change).

THE CALIBRATION SPEEDS

The calibration register which controls changes in target is shown inFIG. 18. The calibration register consists of three registers referredto as the tweeker, the tweek factor and the adjuster. The tweeker andthe adjuster are 8-bit registers. The tweek factor, used in case 1 and 3described in the preceding section, can have a value of 2, 3 or 4.Whenever the tweeker overflows or underflows, the tweek factor is addedto or subtracted from the value in the adjuster. Whenever the adjusteroverflows or underflows, target is incremented or decremented. The tweekfactor is a function of the programmed calibration speed, and the speedat which target is changed thus depends on the calibration speed.

Every fourth beat, when the evoked response is measured, the value inthe tweeker register is increased or decreased. This applies only tocases 1 and 3. For case 2, it will be recalled that pacing is at theminimum rate, and target should increase rapidly. The value stored inthe minimum rate tweek register is also a function of calibration speed,but it controls much larger adjustments to the value stored in theadjuster register. Thus overflows from the calibration register occurmore rapidly, and target is made to increase much faster, than in case3. The minimum rate tweek is 16 times greater than the tweek factor forany given calibration speed. (Target is increased in case 2 more than 16times faster than it is in case 3; this is because in case 3 the tweekfactor is added to the adjuster register only with an overflow from thetweeker register, while in case 2 the minimum rate tweek is added to theadjuster register in every measurement cycle.)

One complication is that the tweek value should not be changed by thesame absolute amount (a decrease in case 1 and an increase in case 3)independent of the pacing rate. It is desired that target change by afixed percentage per hour, based solely on the calibration speed andindependent of the rate. The faster the pacing, however, the morerapidly MRCP samples are taken and thus the faster the increases anddecreases are applied to the tweeker value. It is apparent, therefore,that if target is to change by a fixed percentage over any given periodof time, the value by which tweeker is changed whenever an MRCP sampleis taken must necessarily vary with the rate at which the samples aretaken. [It must be borne in mind that we are not dealing here withchanging the tweeker value in accordance with the value of the MRCP. Thevalue of the MRCP is used to control the pacing rate. We are talkinghere about changing the tweeker value in order to control a change inthe value of target, solely to compensate for system drifts. As such,the amount by which tweeker is changed on every fourth beat is afunction of rate only and is independent of MRCP.] Toward this end arate table is provided, as shown symbolically in FIG. 18. A rate of 40pulses per minute might have a corresponding value of 15, and a rate of150 pulses per minute might have a corresponding value of 4 in thetable. What this means is that the higher rate causes the tweeker valueto be changed by a lesser amount each time. Because the rate and valueentries in the table have an inverse relationship, the rate of which thetweeker value is changed remains constant over time. [The pacer requiresa table to convert between rate and escape interval anyway, the escapeinterval being an inverse function of the rate. The same table can beused since the same inverse relationship applies to both.]

A slow calibration speed is applicable to an active patient who is nottaking any drug therapy (or who may be taking drug therapy, butinfrequently (once or twice per day)). For such a patient, target canchange by about 10% per hour when the pacer is operating in cases 1 and3. The medium calibration speed applies to drugs which reach peak serumlevel over a moderate period of time, i.e., drugs taken every 4-6 hours.This is the default case, and target can change by about 15% per hour.Finally, a fast calibration speed is applicable to a patient who takesdrugs which reach peak serum level very quickly, i.e., drugs taken every2-4 hours. In such a case, target can change by about 20% per hours.

OVERDRIVING IN ORDER TO PACE

When the rate-response function is enabled, the pacer measures the RCPevery fourth cycle and uses (MRCP-target) to control the pacing rate.The RCP is measured only every fourth cycle in order to save power andincrease rate stability. If the present RCP is smaller than target, therate is increased (5 ppm every fourth cycle) until RCP equals target orthe programmed maximum rate is obtained. If the present RCP is greaterthan target, than the rate is decreased (5 ppm every fourth cycle) untilit equals target, or until the programmed minimum rate is obtained.

In the illustrative embodiment of the invention, the RCP is thedepolarization gradient of the evoked potential. This means that pacingmust occur in order to measure the RCP. If the intrinsic ventricularrate becomes faster than the pacing rate (which pacing rate isestablished by the RCP measurement), then sensed events will inhibitpacing pulses. (The illustrative embodiment of the invention allows rateresponse only in the VVI mode.) If there is an intrinsic beat during acycle in which the RCP is to be measured, the measurement cannot betaken. In order to take a measurement, the pacer increases its rate by 5ppm every fourth cycle until the intrinsic rate is exceeded and anoutput pulse is issued. (Although the rate is increased only everyfourth cycle in order that there not be too abrupt a change, an attemptis made to measure the RCP during every cycle, rather than just everyfourth cycle, in the case of overdrive.)

Once a pacing pulse is generated, an MRCP value is taken and the pacingrate is adjusted accordingly. The adjustment which is made is based onthe rate which was in effect prior to the last 5 ppm increase thatresulted in a pacer output, i.e., when the pacer rate was within 5 ppmbelow the intrinsic rate.

There is one complication, however, and that is that an additional 5 ppmdecrease in rate is provided in order to allow intrinsic conduction, ifstill present, to be sensed. This 5 ppm decrease is applied only in thecycle which immediately follows that in which the RCP measurement istaken; it is during this cycle that an extended pacing interval isneeded in order to allow sensing of intrinsic conduction if it ispresent, If intrinsic conduction is sensed, pacer timing is initiatedfrom the sensed intrinsic event and the extended pacing interval is nolonger needed.

The reason for this variation can be appreciated by considering aspecific example. Suppose that the patient's heart is beating at justabove 70 beats per minute, in which case just under 860 millisecondsseparate successive atrial beats, and successive ventricular beats. Inorder to take an MRCP sample, i.e., in order to issue a pacing pulse, itis necessary to increase the pacing rate to 75 ppm, corresponding to anescape interval of 800 milliseconds. There are still 860 millisecondsseparating P waves. By decreasing the escape interval to 800milliseconds during the first cycle which follows sensing of anintrinsic beat, the pacing pulse is 60 milliseconds closer to the next Pwave than an intrinsic beat would be were it allowed to occur. Since theP waves are still occurring at the rate of 70 per minute, if the pacingrate is dropped back to 70 ppm immediately following the sensing of anevoked potential with the escape interval now reverting back to 860milliseconds, the next pacing pulse will be 60 milliseconds closer tothe next P wave than it otherwise would be because the preceding pacingpulse was this much closer to the preceding P wave. This might very wellmean that a pacing pulse is issued when an intrinsic beat wouldotherwise be sensed. It is to avoid this situation that the pacing rateis decreased by 5 ppm for a single cycle after the sensing of an evokedpotential when the pacer has to overdrive the intrinsic rate in order totake an MRCP sample.

There are three sequences which govern overdrive pacing of this type.The highest rate before overdrive will be referred to herein as thepre-overdrive rate. The three sequences are as follows:

(1) If the RCP measurement indicates that no rate adjustment isnecessary (MRCP=target), the pacer initially decreases its rate by 10ppm for one cycle (5 ppm to compensate for the 5 ppm overdrive, and anextra 5 ppm to allow an intrinsic beat to occur in the next cycle), andthen increase its rate by 5 ppm (to cancel the extra 5 ppm) so that therate is maintained within 5 ppm below the intrinsic rate. [Thus if thepre-overdrive rate was 70 ppm and the rate had to be increased to 75 ppmin order to take a sample, in the cycle following taking of the samplethe rate is decreased to 65 ppm, and in the next cycle it is returned to70 ppm.]

(2) If the RCP measurement indicates that rate should be increased (MRCPis less than target), the pacer initially decreases its rate by only 5ppm for one cycle, and then increases its rate by 5 ppm in order toreturn the rate to the value in effect when the overdrive output pulsewas issued. In the case of a pre-overdrive pacing rate of 70 ppm, therate is increased to 75 ppm in order to generate a pacing pulse so thatthe evoked potential can be sensed. In the next cycle the rate isdecreased to 70 ppm, and in the following cycle it is increased to 75ppm.

(3) If the RCP measurement indicates that a reduction in rate is needed(MRCP is greater than target), the pacing rate is initially decreased by15 ppm (the additional 5 ppm compared to case (1) is due to themeasurement requirement of a rate reduction) and then increased by 5 ppmto bring the rate within 10 ppm below the intrinsic rate. [If thepre-overdrive rate was 70 ppm and the rate was increased to 75 ppm inorder to pace the heart, then in the cycle following sensing of theevoked potential the rate is decreased to 60 ppm, and in the next cycleit is increased to 65 ppm.]

Whether rate response is enabled can be programmed by the physician. Twotiming cycles with rate response on are illustrated in FIGS. 14 and 15.(Throughout the timing cycle drawings, the darkened area of each cycledepicts the usual refractory period.) The former is a case whereoverdrive is not necessary. The latter is a case in which intrinsicactivity affects the RCP measurement.

As shown in FIG. 14, after the patient starts to exercise, the need toincrease the pacing rate is detected in the second cycle when themeasured RCP is found to be smaller than target. Between the second andthird cycles, the pacer increases its rate by 5 ppm; the escape intervalthus decreases by about 57 milliseconds between the second and thirdcycles. The pacer maintains the rate at this level until the RCP ismeasured again four cycles later.

During the sixth cycle it is found that the RCP is still smaller thantarget. The pacer increases its rate once again by 5 ppm, with theescape interval decreasing to 750 milliseconds between the sixth andseventh cycles. The RCP measurement in the tenth cycle indicates thatthe rate is still not high enough; MRCP is still smaller than target,and the pacer increases its rate once again by 5 ppm with the escapeinterval dropping to 706 milliseconds.

With cessation of exercise in the eleventh cycle, the need to decreasethe rate is reflected in the next RCP measurement at the beginning ofthe fourteenth cycle. The measured RCP is now found to be larger thantarget. Therefore, the pacer decreases its rate by 5 ppm, and the escapeinterval rises to 750 milliseconds between the fourteenth and fifteenthcycles.

The effect of sensing intrinsic activity during rate response isillustrated in FIG. 15. The patient's sinus rate is 71 beats per minute,faster than the initial pacing rate of 70 pulses per minute. At thestart of the third cycle an RCP measurement is due, but it cannot bemade because the sensed intrinsic activity inhibits the generation of anoutput pulse. To overcome the intrinsic rate and to allow an outputpulse to be issued, the pacing rate increases by 5 ppm between the thirdand fourth cycles. With the pacing rate increasing from 70 to 75 ppm,the pacing rate is now faster than the intrinsic rate and an outputpulse is generated at the start of the fourth cycle. An RCP measurementis now made and it is found that the measured value of RCP is equal totarget.

This is an example of the first overdrive case described above: in thecycle following the measurement, the pacing rate is decreased by 110ppm, and it is then increased by 5 ppm in the next cycle. Thus the V-Rinterval between beats four and five in FIG. 15 is shown as 890milliseconds, corresponding to a rate of 67 ppm. The R-R interval duringthe next cycle is 845 milliseconds, corresponding to an intrinsic rateof 71 ppm. The pacing rate is maintained at 70 ppm, within 5 ppm of theintrinsic rate. The next RCP measurement which is due in the seventhcycle (four cycles after the initial RCP measurement attempt was made,not four cycles after success was achieved), cannot be taken becauseintrinsic activity is sensed once again. The pacing rate is againincreased by 5 ppm between the seventh and eighth beats to allow an RCPmeasurement to be taken.

AUTOMATIC OUTPUT REGULATION

In order to conserve energy and minimize distortion of MRCP due to leadpolarization, the amplitude and width of each output current pulse arepreferably such that minimal energy is expended. Toward the end, athreshold search is conducted periodically to determine the pacingthreshold. The output values are automatically adjusted accordingly, anda predetermined safety margin is added. Automatic output regulation canbe programmed on or off, but when it is programmed on a threshold searchis automatically initiated every 54,000 ventricular events; at anaverage rate of 75 ppm, a threshold search is initiated every twelvehours. Exactly how often the search takes place depends on the pacingrate. A threshold search also occurs upon request by the programmer.

Another aspect of automatic output regulation is capture verificationwhich occurs every four cycles. If loss of capture is detected, it isfollowed by an adjustment of the output and a vertical of capture on abeat-by-beat basis until capture is regained and a predetermined safetymargin is added. During every cycle in which loss of capture isdetected, a 10-milliampere, 1-millisecond back-up output pulse isissued. Capture verification can result only in an increase of outputenergy. A decrease can occur only during a threshold search.

It should be noted that it loss of capture occurs during an RCPmeasurement cycle, then the RCP will appear to be smaller than target,thus causing an increase in rate. Therefore, during lead maturation(when intermittent loss of capture due to lead dislodgement mostfrequently occurs), automatic output regulation should be programmed onif rate response is programmed on. This allows the automatic outputregulation function to detect the loss of capture; rate response issuspended, as will become apparent below, until capture is regained.

During automatic output regulation (both threshold searches and captureverification), output values are increased according to the horizontalsteps listed in the table of FIG. 11. The starting pulse width, aprogrammed parameter, is one of five possible values. Each outputincremental step includes both a current amplitude and a pulse width.For example, with a starting pulse width of 0.4 milliseconds, the lowestenergy output pulse has an amplitude of 1 milliampere and a pulse widthof 0.4 milliseconds. For any starting pulse width, the incremental stepsfollow first a vertical and then a horizontal line. Thus in the caseunder consideration, the starting pulse width remains the same but thecurrent amplitude increases up to 5 milliamperes. Thereafter, thecurrent amplitude remains at 5 milliamperes while the pulse widthincreases in 0.1-millisecond steps up to the maximum of 1.0milliseconds.

What is shown in FIG. 12 is an illustration of how the pacer changes theoutput pulse in order to regain capture when loss of capture is detectedat an output setting of 3 milliamperes and 0.1 milliseconds. The pulsewidth is first maintained constant until the output current amplitude isincreased to 5 milliamperes. Then the current amplitude remains constantas the pulse width is increased. As will be described below, aftercapture is verified once again, the output values are increased by twosteps in order to provide a safety margin. If the output values reach 5mA/1.0 ms without capture being regained, or if capture is regained butwhen the threshold has the safety margin added to it the values exceed 5mA/1.0 ms, the pacer automatically initiates State Set pacing at 10mA/1.0 ms.

Another sequence is illustrated in FIG. 11, this one representing athreshold search with a starting pulse width of 0.2 ms. During athreshold search the initial current amplitude is always 1 mA. The firstfour incremental steps involve increasing the current amplitude whilemaintaining the pulse width at the programmed starting value.Thereafter, it is the pulse width which is incremented. Once again, ifthe threshold plus safety margin values exceed 5 mA/1.0 ms, the pacerautomatically initiates Stat Set pacing at 10 mA/1.0 ms.

There are two cases of automatic output regulation which must beconsidered, capture verification and threshold search.

CAPTURE VERIFICATION

Capture verification occurs every fourth cycle (when intrinsic beats arenot in control). Thus when automatic output regulation is programmed on,loss of capture cannot occur for more than three consecutive cycleswithout a back-up pulse being issued. If rate response is alsoprogrammed on, capture verification occurs in conjunction with the RCPmeasurements, during every fourth cycle.

Once loss of capture is detected, the pacer performs captureverification during each succeeding cycle, not every fourth cycle, untilcapture is regained and the new output values have been determined. Thepacer verifies cardiac capture through detection of an evoked responsefollowing the generation of a pacing pulse. Loss of capture is definedby an evoked response not being detected within 60 millisecondsfollowing an output pulse. When loss of capture is detected, the pacerissues a back-up pulse (10 mA/1.0 ms) 60 milliseconds after the initialoutput pulse; a primary purpose of the back-up pulse is to insure thatthere is a beat. The loss of capture results in rate response beingsuspended; also, the present pacing rate is increased by 5 ppm in orderto eliminate possible fusion beats. (Fusion beats make captureverification very difficult.)

If loss of capture is detected in the next pacing cycle, the back-upoutput pulse is again issued 60 milliseconds after the ordinary pacingpulse, and the pacing rate is again increased by 5 ppm. The totalincrease of 10 ppm above the rate in effect when loss of capture wasdetected is designed to eliminate fusion beats if that is what wasoccurring.

If capture is detected during either of the two cycles following thecycle in which loss of capture was detected, then rate response isresumed, an RCP measurement is taken, and the rate is adjustedaccordingly. But if capture is not detected in either of these twocycles, the output values are increased by one step each cycle untilcapture is detected. Pacing is maintained at the elevated rate of 10 ppmover the rate in effect when loss of capture was first detected untilcapture verification is complete.

Once capture is regained, the output values are kept constant untilcapture is verified for three consecutive cycles. Then the pacer issuesan ECG "signature" which consists of two output pulses, each at 10mA/1.0 ms, 60 milliseconds apart. The ECG signature indicates thatcapture has been regained. The purpose of the signature pulses is toavoid confusion on the part of a person analyzing an ECG trace. Oncecapture has been verified, the output values are incremented by twosteps to establish a safety margin. As mentioned above, if with thesafety margin the maximum output values, for evoked response detection(5 mA/1.0 ms) would be exceeded, Stat Set pacing is initiated (10 mA/1.0ms) and automatic output regulation is disabled. Automatic outputregulation resumes only if the automatic output regulation is programmedon once again. With Stat Set pacing, rate response is also disabled, ifit was programmed on in the first place. The reason for this is that theevoked potential waveform is distorted by large-magnitude Stat Setpacing pulses.

If capture is regained, the new output values (threshold plus safetymargin) are first reflected in the cycle following the ECG signature,and they remain in effect until the threshold search is initiated againor loss of capture is again detected for three consecutive cycles. Ifrate response is programmed on, the pacer resumes rate response once thenew output values are determined. If rate response has been programmedoff, the pacer returns to the programmed minimum rate in the cyclefollowing the ECG signature cycle.

With respect to increasing the rate in order to avoid fusion beats, therate cannot exceed the programmed maximum rate, if rate response isprogrammed on. If rate response is programmed off, the rate cannotexceed 100 ppm, or 15 ppm plus the programmed minimum rate, whichever isgreater. (This is the definition of maximum rate in this case.) Wheneverthe rate has been increased to its maximum allowable level, captureverification continues but rate increases are not allowed.

The capture verification function is illustrated in FIG. 16. In thesecond cycle, an evoked response is not detected during the60-millisecond capture verification window which follows the initialoutput pulse. This causes a back-up output pulse (10 mA/1.0 ms) to beissued 60 milliseconds after the ordinary pacing pulse. The refractoryinterval is reinitiated. In order to avoid fusion beats if that was theproblem, the rate is increased by 5 ppm, with the escape interval thusdecreasing from 857 milliseconds to 800 milliseconds. If rate responsewas programmed on, it is suspended as soon as loss of capture isdetected.

In the third cycle, the ordinary output pulse again fails to obtaincapture. A back-up pulse is issued, the refractory interval isre-initiated, and the rate is again increased by 5 ppm. In the fourthcycle, failure to obtain capture is detected for the third consecutivetime. After the back-up pulse is issued and the refractory interval isreinitiated, the output values, which initially are 4 mA and 0.2 ms, areincreased one step to 5 mA/0.2 ms (see table of FIG. 11, row 2, column4).

In the fifth cycle, the increase in output results in capture by theordinary output pulse. The present output values of 5 mA/0.2 ms continueto achieve capture in the next two cycles. Because capture is verifiedfor three consecutive cycles (cycles 5, 6 and 7), an ECG signature isissued in the eighth cycle, two output pulses, each at 10 mA/1.0 ms, 60milliseconds apart.

The establishment of a safety margin is reflected in the ninth cycle.The safety margin is an increase in output by two steps, in this casefrom 5 mA/0.2 ms to 5 mA/0.4 ms. Capture verification at the new outputvalues continues in cycles 9, 10 and 11. In the twelfth cycle, rateresponse is resumed, the RCP is measured, and the pacer adjusts its rateaccordingly. Thereafter, RCP measurements and capture verification occurevery fourth cycle.

THRESHOLD SEARCH

When automatic output regulation is first programmed on, a thresholdsearch is initiated to determine the pacing threshold and toautomatically set the output parameter values accordingly. (Thisincludes the usual safety margin of two steps.) After the initialdetermination, the threshold search is performed automaticallyapproximately every twelve hours, and whenever it is initiated by theprogrammer.

When the threshold search is initiated, the ECG signature is issued. Thepacer increases its present rate by 5 ppm, suspends rate response,lowers the output current to 1 mA, and sets the pulse width to theselected programmed starting value. The current is lowered to 1 mAbecause the object of the threshold search is to use the lowest possiblecurrent amplitude. If capture is not obtained at the lowest outputsettings, a back-up output pulse is issued 60 milliseconds after theinitial output pulse. The pacing rate is again increased by 5 ppm andthe output current is increased to 2 mA. If capture is not obtained atthese output settings, a back-up pulse is issued and the output currentis increased by 1 mA (up to a maximum of 5 mA) each cycle until captureis obtained. (There are no more rate increases, however.) The pacingrate is maintained at the elevated level (10 ppm above the rate ineffect when the threshold search was initiated) until the thresholdsearch is completed. If capture cannot be obtained at 5 mA and thestarting pulse width value, the pacer increases the pulse width by 0.1ms (up to a maximum of 1.0 ms) every cycle until capture is obtained.Back-up pulses continue to be issued in each cycle in which capture isnot obtained. It will be apparent that the threshold search sequence isvery similar to the capture verification sequence, with the majordifference being that the capture verification sequence begins with thepresent output values of current amplitude and pulse width, whereas thethreshold search always begins with the lowest possible currentamplitude and the programmed starting pulse width.

Once capture is obtained, the output values are kept constant untilcapture is verified for three consecutive cycles. An ECG signature isthen issued to indicate the end of the threshold search, and the pacerincreases its output values by two steps to establish a safety margin.Once again, if the two steps take the output values beyond 5 mA/1.0 ms,Stat Set pacing takes place (fixed rate at 70 ppm, with pulses havingthe back-up output values).

Following capture, the new output values (with safety margin) are firstreflected in the cycle following the ECG signature and remain in effectuntil the next threshold search is initiated or loss of capture isdetected for three consecutive cycles. The pacer resumes rate response,measures the RCP, and adjusts its rate accordingly in the fourth cyclefollowing the ECG signature cycle. If rate response has been programmedoff, the pacer returns to the programmed minimum rate in the cyclefollowing the ECG signature cycle.

If intrinsic activity is sensed during the threshold search, the searchis temporarily suspended and the pacer increases its rate by 5 ppm eachcycle until a pacer output pulse is issued. The reason for this is thata threshold search cannot possibly be conducted in the absence of pacingpulses. Once pacing starts to take place, the threshold search iscontinued at the rate in effect when pacing pulses started to be issued.

While the rate is being increased automatically in this manner, it isnot allowed to exceed the programmed maximum rate, if rate response ison. If rate response is off, the rate is not allowed to exceed 100 ppm,or 15 ppm plus the programmed minimum rate, whichever is greater. If therate is increased to its maximum allowable level, the threshold searchwill continue as long as pacing is in effect, but further rate increasesare not allowed. If there are 25 cycles of intrinsic beats or noisebeyond the allowable threshold, the threshold search is canceled, rateresponse is resumed (or the pacer returns to the programmed minimum rateif rate response is off,) and the output returns to the values that werein effect when the search was initiated.

The threshold search function is illustrated in FIG. 17. In the secondcycle, the ECG signature of two output pulses, at 10 mA/1.0 ms, issued60 milliseconds apart, indicates the initiation of a threshold search.The present pacing rate is increased by 5 ppm and rate response issuspended, assuming that it was programmed on in the first place.

In the next cycle, an output pulse is issued at the lowest outputcurrent value, 1 mA, and the selected starting pulse width value, inthis case an assumed value of 0.2 ms. This output pulse fails to obtaincapture and a back-up output pulse of 10 mA/0.1 ms is issued 60milliseconds after the initial output pulse. The refractory interval isre-initiated, the rate is increased by 5 ppm, and the output values areincreased by one step, from 1 mA/0.2 ms to 2 mA/0.2 ms.

In the fourth cycle, the output pulse issued at 2 mA/0.2 ms also failsto obtain capture and a back-up output pulse is issued 60 millisecondsafter the initial output pulse. The rate remains at the elevated levelof 10 ppm above the rate which was in effect when the search wasstarted, and the output values are increased by one step. The new outputpulse, issued in the fifth cycle, is shown as succeeded in obtainingcapture.

The output values are maintained at the 3 mA/0.2 ms setting untilcapture is verified for three consecutive cycles, the fifth, sixth andseventh. Then an ECG signature is issued in the eighth cycle to indicatethe end of the threshold search. The establishment of a safety margin(output values increased by two steps, from 3 mA/0.2 ms to 5 mA/0.2 ms)is reflected in the ninth cycle. In the twelfth cycle, rate response isresumed, the RCP is measured, and the pacer rate is adjustedaccordingly. Thereafter, RCP measurements and capture verification occurevery fourth cycle.

THRESHOLD SEARCH HIGH-LEVEL FLOW-CHART--FIG. 29

The flow chart of FIGS. 19-28 is very detailed and will be describedbelow. At this point it will be useful to consider the flow chart onFIG. 29, however, for two reasons. First, it represents the thresholdsearch which has just been described and accordingly a consideration ofthe flow chart at this time will help in the understanding of thethreshold search. The second reason for considering the flow chart ofFIG. 29 is to gain an appreciation of the difference in levels of flowcharts such as that of FIG. 29 and that of FIG. 19-28. The flow chart ofFIG. 29 includes a step such as "capture verified three times?". Theactual programming of a pacer may entail repetition of the same basicloop over and over again, with different steps being executed each timedepending on what transpired during the preceding loops. Yet what isoften necessary for an understanding of the functional pacing steps isnot what goes on during each pass through the loop, but rather what isgoing on in terms of pacing functions. It is often easier to understanda system operation in terms of higher level functional steps then it isin terms of lower level operational steps.

Referring to FIG. 29, whenever a threshold search is to be conducted,rate response is first disabled. The ECG signature is then generated,and the starting output values for a pacing pulse are set (1 mA andprogrammed starting pulse width). The rate is increased by 5 ppm to giveprecedence to paced events over intrinsic events.

A test is then made to determine whether there have been 25 beats ofnoise or intrinsic activity during the search. If the answer is in theaffirmative, the threshold search is aborted. The output values(amplitude and pulse width) are returned to the previous values. If rateresponse is off, rate returns to the minimum rate. Rate response is thenenabled if it has been programmed on, and an exit is made from theroutine.

On the other hand, if there have not been 25 beats of noise or intrinsicactivity, a check is made for an intrinsic R wave. What this means isthat the pacer waits until expiration of the escape interval andgenerates a pacing pulse, if an intrinsic R wave is not detected.However, if an intrinsic R wave is sensed, no output pulse is generated.Instead, a check is first made to see if the current rate is equal tothe maximum rate. [The test whether rate is equal to the maximum rateonly applies if rate response is on. If rate response is programmed off,the rate cannot exceed 100 ppm, or 15 ppm above the minimum rate,whichever is greater.] If it is not, the rate is increased 5 ppm in anattempt to control pacing so that the threshold search can be conducted.If the rate is already at the maximum rate, however, the rate is notincreased. This process continues until the rate is high enough to allowan output to be generated. The pacer then checks whether that pulsecaptures the heart.

In the absence of capture, a back-up pulse is generated after 60milliseconds to insure that the patient is supported. It will berecalled that the rate is increased by a total of 10 ppm at the start ofthe threshold search in order to minimize the incidence of fusion beats.If the present output has an amplitude of 1 milliampere, it is anindication that the first pulse in the search has been generated. Therate is increased by another 5 ppm, for a total of 10. During the nextpass through the loop, the output amplitude will not be 1 milliampere,and another rate increases will not take place.

It is now that the output values are increased by one step. Recallingthat the sequence of increases is such that the amplitude increases tothe maximum of 5 milliamperes before the pulse width increases, a testis made to see if the amplitude is less than 5 milliamperes. If it is,the current amplitude is incremented. A return is then made to the topof the main processing loop, to the beginning of a new cycle.

On the other hand, if the current amplitude is 5 milliamperes, the nextstep must take place in the pulse width. If the pulse width is less than0.8 milliseconds, the pulse width is increased by 0.1 milliseconds, anda return is made to the top of the loop.

If the pulse width is 0.8 milliseconds, however, it is assumed thatcapture cannot be obtained at less than the maximum pulse energy.Accordingly, the amplitude is set at 10 milliamperes and the pulse widthis set at 1 millisecond. In such a case, Stat Set pacing takes place sothe rate is set to 70 ppm (the new minimum rate), and the loop isexited. It should be noted that rate response is not enabled since rateresponse measurements are not considered valid when the pacing pulseshave maximum energy.

The above discussion assumed that capture was not obtained. If captureis detected, the next test is to see whether capture has not only beenverified this time through the loop, but whether it has been verifiedfor a total of three times. Capture is verified three times to insurethat a reliable threshold has been determined and to reduce thepossibility of fusion beats causing a false indication of capturethreshold. If the answer is in the negative, a return is made to the topof the loop without the output being increased in energy. The outputwill be increased once again only if capture is not verified during acycle before three successive captures take place.

If capture is verified three times in succession, the threshold has beendetermined. The output is incremented by two steps as a safety margin,and the signature is generated. A test is now made to see whether rateresponse has been programmed on. If it has not, the rate is set to theminimum rate and the loop is exited. Otherwise, rate response is enabledbefore exiting the threshold search.

There is one more step indicated at the bottom of the flow chart priorto enabling rate response, and that is that the RCP sample time isdetermined if rate response has been programmed on. The depolarizationgradient is processed twice during each cycle when it is examined.First, it is checked 60 milliseconds after the generation of an outputpulse to see whether there has been capture, i.e., whether thedepolarization gradient has a sufficient amplitude to indicate capture.But this is not the amplitude which is used as the MRCP. The MRCP is themaximum amplitude depicted in FIG. 6. It is possible to continuouslysample the depolarization gradient, at 2-millisecond intervals, forexample, for perhaps 130 milliseconds after the generation of an outputpulse in order to see where the maximum occurs, and to use that maximumas the MRCP. But taking so many samples during each cycle would requirethe expenditure of considerable energy. Rather than do this, after thethreshold search it is determined when during each of two cycles thepeak of the depolarization gradient occurs. The MRCP is measured only atthis time during each subsequent cycle in which a measurement is taken.

The MRCP sample is taken somewhere between 70 and 130 millisecondsfollowing the generation of an output pulse. During the two cyclesfollowing the threshold search, the depolarization gradient is measuredevery 2 milliseconds, starting with 70 milliseconds subsequent to thegeneration of an output pulse. Suppose that the peak value is obtained90 milliseconds following the generation of the output pulse. In such acase, during every cycle when an MRCP sample is taken, thedepolarization gradient is examined only twice--60 milliseconds afterthe generation of the output pulse to see if the magnituide issufficient to represent an evoked response, and 90 milliseconds afterthe generation of the output pulse when the maximum value is expected.(The value at 90 milliseconds is not used to determine whether there hasbeen an evoked response because it is desired to generate a back-uppulse, if one is needed, no later than 60 milliseconds after thegeneration of an output pulse.)

TARGET INITIALIZATION--FIG. 30

The high-level flow chart of FIG. 30 depicts a target initializationprocedure. The detailed steps required for the initialization processare shown in the low-level flow chart of FIGS. 19-28. The reason forthis is that once it is understood how the high-level steps such asthose involved in the threshold search of FIG. 29 can be implemented ina low-level detailed flow chart such as that of FIGS. 19-28, it will beapparent to those skilled in the art how to similarly implement thesteps in the high-level initialization flow chart.

The three rules which are used to adjust target were described above. Avalue of target is first determined by the initialization process, aprocess which is automatically activated when rate response isprogrammed on. (Target initialization also occurs when a new minimumrate, output current or pulse width is programmed, or when automaticoutput regulation is programmed on or off while rate response is on.) Itis thereafter that the pacer continuously makes adjustments to the valueof target in accordance with the three rules which comprise thetarget-adjustment algorithm. The initialization process is shown in FIG.30.

The initial value of target should be determined while the patient is atrest, i.e., when the RCP is not being affected by emotional or physicalstress. If initialization is performed while the patient is underemotional or physical stress, the target RCP will be established at toolow a level and may not allow an appropriate rate response. However, theeffect is only temporary because the automatic calibration functioneventually adjusts target to the appropriate minimum-rate level. Forthat matter, target will eventually be adjusted correctly even in theabsence of an initialization process.

During initialization, the RCP is measured for a number of paced cyclesin order to establish a value for target. If intrinsic activity issensed during the initialization process, initialization is temporarilysuspended and the rate is increased by 5 ppm every cycle until pacingresumes.

The first test which is made is to see whether intrinisic R waves arebeing sensed. As indicated at the top of the flow chart, if an intrinsicbeat takes place, the rate is increased by 5 ppm unless the rate isalready at the maximum. (Maximum rate in the flow chart of FIG 30 hasthe same meaning as maximum rate in the flow chart of FIG. 29.) Only ifa paced beat takes place does the system move on to determine the RCPsample time as indicated in the flow chart.

The actual determination of the RCP sample time is the same as thatdiscussed above in connection with the flow chart of FIG. 29. Thedepolarization gradient is examined every 2 milliseconds until it isdetermined when following an output pulse a maximum value is obtained.Thereafter, that is the RCP sample time.

In connecting with both of FIGS. 29 and 30, two measurements areactually taken in order to determine the RCP sample time. In thisregard, it will be helpful first to consider the next sequence in theflow chart of FIG. 30, the determination of an initial value of RCP. Asshown in the flow chart, after the RCP sample time is determined, ameasurement is taken of the RCP. The latest RCP value is subtracted fromthe preceding value, and the difference is examined. IF the differenceis not large, it is assumed that the two measurements have validity andthe processing proceeds. On the other hand, if the difference exceeds athreshold value (determined by the particular measurement systeminvolved), another RCP value is taken. In all cases, the most recentvalue is subtracted from the preceding one, until two successive valueswhich are approximately equal are obtained. The most recent of those twosamples is taken as the applicable RCP value.

In exactly the same way, the RCP sample time is determined, although itis indicated as only one step in each of FIGS. 29 and 30. Successive RCPsample times are determined until two successive measured values areclose enough together for it to be assumed that a sufficient level ofaccuracy has been achieved. The most recent of the two values is takenas the RCP sample time.

Returning to the flow chart of FIG. 30, at least four cycles arerequired to determine the RCP sample time and to determine an initialvalue of RCP. During the next 16 paced cycles, RCP measurements aretaken. It should be noted that to speed up the initialization process,samples are taken every cycle, not every fourth cycle. Furthermore,target is calibrated at an accelerated speed. The calibration speed isthat applicable to Rule 2, rather than that applicable to Rules 1 and 3.

Any measurement system necessarily has a range outside of which valuesare not considered to be accurate. If during the derivation of targetthe measured RCP is not out of range, a double pulse signature isgenerated, and rate response is enabled.

On the other hand, if the target RCP is out of range, a status flag isset to indicate this condition. The status flag allows the RCPout-of-range condition to be telemetered out to a programmer. With theRCP out of range, Stat Set pacing takes place, as indicated at thebottom of FIG. 30. Rate response is not enabled (nor is automatic outputregulation).

DETAILED FLOW CHART-FIGS. 19-28

The pacer output module heading block shown at the top of FIG. 19 isentered from those parts of the flow chart labeled A, as will bedescribed below. The pacer output module is entered when a spontaneousbeat has not been sensed and a stimulus is to be issued. It is notcertain, however, that there has been no intrinsic beat. It is possiblethat there was an intrinsic beat, but that it was masked by noise. It isfor this reason that the first test which is performed is to determinewhether noise was sensed during the preceding cycle.

If it was, a noise flag is set and a noise marker is output by thetelemetry circuit. Three markers can be output for recording on an ECGtrace. The markers represent an output pacing pulse, noise and a sensedevent. If it is determined that noise was not sensed during thepreceding cycle, then as indicated in FIG. 19 the noise flag is reset.Instead of outputting a noise marker, a pace marker is generated inanticipation of the pacing pulse which is about to be issued.

If a pacing pulse is applied to refractory tissue, an evoked potentialwill not be sensed and it is possible for the pacer to think that therehas been a loss of capture when in fact there has been no such thin. Toavoid this, when noise is sensed capture detection and automatic outputregulation are suspended. (That is why the noise flag is set, as willbecome apparent below.) Instead, pacing takes place with the largestpossible output which does not distort the evoked response to the pointat which the RCP cannot be measured accurately. (RCP measurements aretaken even in the presence of noise.) Consequently, as indicated on FIG.19, if automatic output regulation has been enabled, the outputamplitude is set at 5 milliamperes and the pulse width is set at 1millisecond. On the other hand, if automatic output regulation has notbeen enabled, then the output amplitude and the pulse width are set towhatever settings have been programmed by the physician. Similarly, inthe absence of noise, the current settings--whether set by the physicianin the absence of automatic output regulation, or automaticallydetermined if automatic regulation has been enabled--are used togenerate the pulse.

As will be described below, there are several points in the flow chartat which it is determined that it is necessary to generate a back-uppulse. These points are indicated by the letter B. As shown in FIG. 19,the back-up pulse module heading block is entered at such a point in theflow chart, at which time the output amplitude is set at 10 milliamperesand the pulse width is set at 1 millisecond.

As will become apparent below, there are several points in the programat which it is determined that it is necessary to generate an ECGsignature--two pulses, 60 milliseconds apart, each having an amplitudeof 10 milliamperes and a pulse width of 1 millisecond. Before the outputpulse is actually generated, the signature flag is examined to see if itis set. If it is, the back-up pulse output values are set even if otheroutput value settings were previously established.

The flow chart proceeds to the top of FIG. 20 at which point blanking isstarted. This is the conventional step by which the sense amplifier isprotected from large pulses. Because the system of the invention alsoincludes an integrator (see FIG. 7) which must be protected, theintegrator is also blanked just prior to generation of the pacing pulse.In the next step the pacing pulse is generated.

The third step in FIG. 20 is the pulsing of the telemetry coil. Thisstep has nothing to do with the invention itself. The telemetry coil ispushed only to tell the programmer that now is an advantageous time toprogram, if programming is required, because pulsing has just takenplace. In some systems programming causes an interruption insensing/placing, especially if the programming takes longer to completethat the escape interval. The interruption time can be minimized bystarting the programming at the beginning of an escape interval.

Two timers are not set. The blanking timer is set at 140 milliseconds;this is the time during which the sensing of intrinsic beats or noise isnot allowed. The charge dump timer is set for 10 milliseconds; this isthe time during which the charge which is stored in body tissues isdissipated (see top left of FIG. 7).

As is by now standard in the pacing art, the microprocessor is put to"sleep" whenever possible in order to minimize power dissipation. Themicroprocessor is awakened by the timing out of a timer or, whenappropriate, upon the sensing of an event. In the present case, themicroprocessor is put to sleep and remains in this state until the firstof the two timers times out.

It is the 10-millisecond charge dump timer which times out first, atwhich time the microprocessor starts to function again and the endcharge dump module is entered. The first step which takes place is thatthe charge dump is stopped. A test is then performed to determinewhether it is time for an evoked response measurement or a signaturepulse. This step requires explanation because it would appear that thereis no connection between the time when an evoked response measurement isnecessary and the time when a signature pulse is to be generated.

An evoked response measurement is made every fourth beat, or every beatduring initialization and threshold searches. Similarly, evoked responsemeasurements are made when there is a loss of capture, or when there isa fusion beat which might be interpreted as a loss of capture. Thesevarious conditions have been described above, and will become apparentbelow. The important thing is to recognize that evoked responsemeasurements are made twice during a cycle--60 milliseconds after thegeneration of an output pulse to determine whether the pulse capturedthe heart, and 70-130 milliseconds after the generation of the pulsewhen the peak depolarization gradient potential is expected. Toward thisend, two timers are set--the capture timer and the RCP sample timer. Itwill also be recalled that the signature consists of two large-amplitudepulses separated by 60 milliseconds. If the signature flage has beenset, one such pulse has already been generated in the second step ofFIG. 20. In order to generate the second pulse, the capture timer isset, and the second pulse is generated upon its timeout. It is for thisreason that the capture timer is set on what would appear to be eitherof two disconnected needs--the need to sense an evoked response, or theneed for a signature pulse. (If it is a second signature pulse which isrequired, the RCP sample timer is still set along with the capturetimer. Since a measured RCP is not accurate in the presence of alarge-amplitude stimulus, the RCP sample timer timeout is ignored, aswill become apparent below.)

The capture sample time is 60 milliseconds. However, by the time thecapture sample timer is set, 10 milliseconds have already gone by sincethe generation of the pacing pulse, as a result of the operation of thecharge dump timer. Consequently, the capture sample timer is actuallyset to 50 milliseconds in order to time out a 60-millisecond capturesample interval. In a similar manner, the RCP sample timer is set to 10milliseconds less than the RCP sample time which is determined duringthe initialization routine.

It might be thought that an RCP sample alone would suffice; it could notonly provide an MRCP value, but it could also serve to verify whetherthere has been an evoked response. However, if there has not been anevoked response it is desired to issue a back-up pulse to support thepatient. Since the RCP sample is taken 70-130 milliseconds after thegeneration of a stimulus, in the event of a fusion beat, perhapsresulting in an MRCP value too low to be recognized as an evokedresponse, a back-up pulse issued 70-130 milliseconds after the stimulusmight actually fall in the T wave, something which is generally to beavoided. If a back-up pulse is to be issued, it should take placeearlier in the cycle when it will not fall in the T wave even if thepacer mistakingly treats a fusion beat as a loss of capture. For thisreason a capture sample after 60 milliseconds is also necessary, and twosamples must be taken each cycle.

After the capture and RCP sample timers are set, the integrator (FIG. 7)is turned on so that the depolarization gradient will be measured andvalues will be available on either timer timeout. The system then goesto sleep, as indicated at the top of FIG. 21 until one of the timerstimes out.

The system then checks whether the capture sample timer has timed out.If not, a check is made whether the blanking timer has timed out. In theevent neither timer times out, a pass is made through the loop at thetop of FIG. 21 once again. Eventually, one of the timers times out.(Although the capture sample timer has a shorter interval than theblanking timer, the former is usually not set, e.g., on 3 out of 4cycles, and it is the blanking timer which usually times out.) If it isthe capture sample timer which times out, the system moves on to thecapture check routine; otherwise, the system moves on to the endblanking routine at the top of FIG. 26. It should be noted that if thereis a capture sample timer timeout at the top of FIG. 21, the blankingtimer is not ignored. The blanking timer timeout is handled in the endblanking module at the top of FIG. 26.

It will be recalled that the capture sample timer is set not only if anevoked response measurement is necessary, but also if a signature pulsepair is required (see bottom of FIG. 20). The first pulse of the pair iscontrolled by the test of the signature flag at the bottom of FIG. 19,followed by the generation of a pacing pulse at the top of FIG. 20. Thesecond pulse is controlled by checking the signature flag once again inthe middle of FIG. 21. When the capture sample timer times out 60milliseconds after the first pulse of the pair is generated, anotherpacing pulse is generated. First the system resets the signature flagsince it is no longer needed. Moving on to FIG. 22, a pace marker isoutputted because another pacing pulse, the second half of thesignature, will be issued. A check is not made to see whether it is timefor a rate increase. Referring to the threshold search routine shown inFIG. 29, it will be recalled that at the start of the search, the pacingrate is increased in two steps of 5 ppm each. The purpose of theincrease is to minimize the possibility of fusion beats. The firstincrease takes place when the second signature pulse is issued. Thereare other times when the rate must be increased, but the only one ofconcern now is when the second signature pulse is to be issued at thestart of a threshold search routine. (The same path through the flowchart is taken when the signature is issued at the end of the thresholdsearch routine; at this time the rate is not increased because there isnot reason to do so.) A check is made to see whether the rate is at amaximum and, if it is not, the rate is increased by 5 ppm. Processingthen resumes at point B in FIG. 19, where the output parameters are setfor actual issuance of the second pulse of the signature pair. The pulseis actually treated as a back-up pulse since they have the same outputvalues.

The way in which the two pulses of the signature pair are generatedillustrates the basic difference between the high-level flow chart ofFIG. 29 and the detailed flow chart of FIGS. 19-28. At the top of FIG.29 there is a single step in which the pulse pair of the signature issaid to be generated. In actuality, it takes two passes through the mainprocessing loop because both pulses are generated in the second step ofFIG. 20. The methodology is easier to understand from a high-level flowchart such as that of FIG. 29, although details of implementation mustbe left to a low-level flow chart.

Returning to FIG. 21, in the usual case, the signature flag set testwill be answered in the negative; this point in the main processing loopis usually reached with timeout of the capture sample timer 60milliseconds after the generation of a non-signature pacing pulse (andusually only on every fourth cycle). A test is then made to see whetherautomatic output regulation has been programmed on. If it has not, abranch is taken to the middle of FIG. 22 where a test is performed tosee whether rate response is enabled. If automatic output regulation ison, on the other hand, a check is now made to see whether there has beenan evoked response; this is accomplished by sampling the output of theintegrator which represents whether or not there has been capture.

At the bottom of FIG. 21, a branch is taken depending upon whether whathas been issued is a back-up pulse. The pacing pulse can be part of thesignature, a back-up pulse or an ordinary stimulus. A back-up pulse isgenerated only when the ordinary stimulus has not captured the heart.Assuming that an ordinary stimulus has been generated, the next testwhich is performed, at the top of FIG. 22, is to see whether the noiseflag has been set. This flag is set at the top of FIG. 19 if noise hasbeen sensed. If noise is present, a test is not made to see whether thecapture limit has been exceeded, i.e., whether the stimulus has capturedthe heart. The reason for this is that the noise may mask what is reallygoing on. As will be described below there is a counter which keepstrack of the number of capture failures (loss of capture). That counteris now reset because the count is not reliable in the presence of noise.The system moves on to the rate response routine which begins in themiddle of FIG. 22.

On the other hand, if the noise flag is not set, thecapture-limit-exceeded test in FIG. 22 is performed. If the capturelimit is exceeded, the loss of capture counter is reset; it will becomeapparent below that the current count is of no importance becausecapture has been regained. But if the capture limit has not beenexceeded, what is required is a back-up pulse since the pacing stimulushas failed to capture the heart. A pace marker is first outputted. Thereason for this is that a back-up pacing pulse will be issuedmomentarily. The system then checks to see whether it is time for a rateincrease. The reason for the test here requires careful understanding.

The reason that a simulus is generated in a fusion beat is that thepacer does not sense the beat, even though it may have just begun. Butthe remaining question is why the evoked potential may not be sensed 60milliseconds later. There are two reasons for this. First, the sensesignal may be on the decrease by the time 60 milliseconds have elapsedafter the output pulse is generated, when the pacer looks to see whetherthere has been capture; that is because depolarization startedearly--even before the stimulus. Second, the sense signal for anintrinsic beat is generally narrower than that for a paced beat, so thatit may be even more difficult to sense capture. Fusion beats may thus beinterpreted as a loss of capture. That is why it is a general approachin the invention to increase the pacing rate during automatic outputregulation in order to minimize the possibility of fusion beats.However, experiments have actually shown that fusion beats may stilloccur often enough to be of concern even when the pacing rate isincreased by as much as 10 ppm during automatic output regulation. It isfor this reason that a unique test has been developed for actuallydetermining whether a fusion beat has occurred, a test which will bedescribed in detail below.

The fact that the capture-limit-exceeded test was answered in thenegative does not necessarily mean that the output parameters of thepacing pulse are not sufficient to capture the heart. It is possiblethat a fusion beat took place, with the result that the capture samplewas too low in magnitude to represent capture. Before the systemincreases the output pulse energy in an attempt to regain capture, ittries to avoid fusion beats in the hope that it will be possible toverify that the present output pulse energy is sufficient. It is forthis reason that the pacing rate is increased twice in succession, 5 ppmeach time. A back-up pulse is about to be issued since capture may havebeen lost and the heart may not have beat, but the rate increase is inpreparation for the next ordinary stimulus which will be generated. Asshown in FIG. 22, the rate is increased by 5 ppm only if the rate is notalready at the maximum. A branch is then taken to point B on FIG. 19 atwhich time a back-up pulse is generated.

Assuming that an ordinary stimulus resulted in the failure of thecapture-limit-exceeded test at the top of FIG. 22, a back-up pulse isnow generated, as just described. From entry point B on FIG. 19, thesystem moves on to the steps shown in FIG. 20. There is another chargedump, and the sense amplifier and integrator are both blanked. At thebottom of FIG. 20, the capture and RCP sample timers are set becauseevoked response measurements are made for back-up pulses. Actually, RCPsamples are not taken because they are unreliable with maximum-energystimuli, but capture samples are taken. On FIG. 21, the auto-output-ontest is answered affirmatively because the only time that back-up pulsesare generated in the first place is when automatic output regulation hasbeen programmed on. At the bottom of FIG. 21, the back-up pulse test isanswered affirmatively, and a branch is taken to the top of the leftpath on FIG. 22.

On FIG. 20, a test is performed whether it is time for an evokedresponse movement. When capture has been lost, a capture sample is takenon all succeeding cycles until the problem is resolved. As justdescribed, an ordinary stimulus results in a pass through the path onthe right side of FIG. 22, the rate is increased by 5 ppm and then aback-up pulse is issued. Following the back-up pulses, a pass is madethrough the left branch of FIG. 22. Then another ordinary stimulus isgenerated, a pass is made through the right branch (assuming that thecapture-limit-exceeded test is failed once again), the rate is increasedby another 5 ppm, a second back-up pulse is generated, and a second passis taken through the left path on FIG. 22. The two 5-ppm increases aredesigned to eliminate fusion beats if that is the problem. It might beexpected that two rate increases in the space of three cycles, wouldsolve the fusion beat problem. We have discovered, however, that theheart can actually exhibit three successive fusion beats, with a 5-bpmrate increase between the first and second, and another 5-bpm increasebetween the second and third. Each pass through the right path of FIG.22 can represent a true loss of capture, or it can represent a fusionbeat. Increasing the pacing rate even by 10 ppm is not enough todistinguish between the two conditions. It is for this reason that thesteps in the left path of FIG. 22 are provided.

As seen at the bottom of FIG. 21, the left path of FIG. 22 is enteredfollowing the taking of a capture sample 60 milliseconds after thegeneration only of a back-up pulse. At the top of FIG. 22, a test ismade to see whether the capture limit has been exceeded, i.e., whetherthe back-up pulse captured the heart. The results of the test are usedin a unique way to tell whether what is going on is a true loss ofcapture or a sequence of fusion beats. Interestingly, capture by aback-up pulse is an indication that what is involved is a loss ofcapture. This paradox will now be explained.

Each back-up pulse is generated 60 milliseconds after an ordinarystimulus. The question to be answered is whether what appears to havebeen a loss of capture was really a loss of capture or simply a fusionbeat (with the result being that the capture sample was too low inmagnitude, as explained above, for the sample to verify capture). If theback-up pulse does not capture the heart now, i.e., the test at the topleft of FIG. 22 is answered in the negative, a logical explanation isthat capture was not just achieved because the heart tissue isrefractory. This in turn means that the heart beat before the back-uppulse was generated. Since an intrinsic beat was not sensed and capturewas not verified following generation of the ordinary stimulus, whatmust have happened is that there was a fusion beat. Consequently, if theback-up pulse does not capture the heart, a fusion beat marker isoutput. The system then moves on to FIG. 23 where the RCP sample timeris stopped. Because large-magnitude back-up pulses cause thedepolarization gradient to be distorted, RCP samples are not takenfollowing the generation of back-up pulses. The microprocessor is thenput to sleep and a branch is taken to point C on FIG. 26; the blankingtimer was set prior to generation of the back-up pulse, and the systemwaits for blanking to end. It should be noted that the rate wasincreased by at least 5 ppm and by at most 10 ppm by the time thecapture-limit-exceeded test at the upper left of FIG. 22 is answered inthe negative. The rate is returned as will be described shortly.

On the other hand, suppose that the test at the top left of FIG. 22 isanswered affirmatively--the back-up pulse did capture the heart. Thismeans that the heart tissue was not refractory, which in turn means thatthe heart did not beat just prior to the back-up pulse. This isinterpreted as a loss of capture on the part of the preceding ordinarystimulus. The fact that a single pulse may not have captured the heartmay or may not be sufficient to control an increase in the outputenergy. Whether it is depends on whether a threshold search is inprogress. If the search is already in progress, a single loss of captureis enough to control a step increase in the output energy, as indicatedin FIG. 22. A test is then made to see whether the maximum output energy(short of a back-up pulse) has been reached. If it has, the systemreverts to Stat Set pacing.

The RCP sample timer is then stopped; the left branch of FIG. 22 isentered because a back-up pulse was generated, and RCP samples are nottaken following the generation of back-up pulses. The microprocessor isthen put to sleep and processing resumes with the end blanking routinewhen the blanking timer times out.

The above description assumed that the threshold-search-in-progress teston FIG. 22 was answered affirmatively. If a threshold search is not inprogress, what it means is that an ordinary stimulus resulted in a lossof capture, as confirmed by a back-up pulse not capturing the heart. Atest is made to see whether a loss of capture has occured three times;this is accomplished by examining the loss of capture counter. (Thereason for resetting the loss of capture counter in the step shown inthe middle of FIG. 22 in the presence of noise, or followingverification of a capture, is that when the loss of capture counterreaches a count of three, the output will be increased until capture isregained, and there is no need for that if capture is regained before atriggering count of three is reached.) If capture failure has not beenverified at least three times, the loss of capture counter isincremented, the RCP sample timer is stopped, and the microprocessor isput to sleep until the end of blanking.

On the other hand, if loss of capture has been verified three times, anumber of times sufficient to guard against an erroneous determinationof loss-of-capture, then what is done is to control an increase inoutput energy. This is a form of threshold search, except that thestarting output energy is the current value. The search is controlled bysetting the search-in-progress flag. Rate response is then disabledbecause it is always disabled when the output pulse energy is in theprocess of being changed. The output is then increased, following whicha test is made to see whether the upper limit has been reached, just asthe test is performed during a threshold search. The RCP sample timer isthen stopped and the microprocess is put to sleep until the end ofblanking. The next time that the path on the left side of FIG. 22 isentered, the threshold-search in-progress test will be answeredaffirmatively.

In the middle of FIG. 22, there is a test to see whether rate responsehas been enabled. At the end of the automatic output regulation routine,whether what has been involved in a periodic threshold search or theroutine which follows an apparent loss of capture, the rate may havebeen increased by 5 ppm or 10 ppm as a result of the effort to avoidfusion beats. This increase should be compensated for. If rate responsehas been enabled, there is no need to do anything because the rate willbe adjusted by the rate response routine to be described below; theartificial increase in rate will be lowered because the rate is too fastfor present physiological needs. As shown at the bottom of FIG. 22, themicroprocessor is put to sleep and the rate response module is entered.When the RCP sample timer times out 70-130 milliseconds after the laststimulus was generated, rate response processing takes place.

On the other hand, if rate response has not been enabled, an adjustmentmust be made for the 5-ppm or 10-ppm increase in rate which may havetaken place. A test is made to see whether a threshold search is inprogress. At the end of the threshold search, as will be describedbelow, the search-in-progress flag is reset. If it is reset and theanswer to the threshold-search-in-progress test is in the negative, theminimum rate is set (it being recalled that the assumption is that rateresponse has not been enabled). On the other hand, if a threshold searchis in progress, the minimum rate is not set, and the system waits forblanking to end.

The top (right branch) of FIG. 23 is reached when an RCP sample is to betaken as a result of rate response being enabled and a stimulus havingbeen generated. It is at this point that the rate is adjusted inaccordance with the measured value of the RCP, and target is adjusted inaccordance with the three Rules enumerated above.

If the measured RCP (MRCP) equals target, then no change in rate isnecessary. The control parameter (MRCP-target) is zero, and this meansthat the present rate is on target. On the other hand, if MRCP does notequal target, a test is performed to see whether the control parameteris positive or negative. A branch is taken to increase the rate by 5 ppmor to decrease it by the same amount. As mentioned above, the advantageof a closed-loop system is that it is not necessary to pre-define whatwould otherwise be a complex relationship between the control parameterand the rate. All that it is necessary to do is to increase or decreasethe rate until the control parameter returns to the desired value.

Whether the rate is increased, decreased or left alone, a test isperformed to see if the rate, after any decrease or increase which mayhave occurred, is equal to the minimum rate. If it is, a branch is takento the left side of FIG. 23. If the rate is not equal to the minimumrate, two tests are performed to verify that the rate, as it may havebeen just adjusted, is within the minimum and maximum limits. If therate is now below the minimum rate, it is increased; if the rate is nowabove the maximum rate, it is now decreased. After such an increased ordecrease, the processing continues at the bottom of FIG. 23, along theleft branch if a minimum rate condition has been obtained, or along theright branch if the rate is between the minimum and maximum limits.

If the system is operating at minimum rate, Rule 2 requires that targetbe increased rapidly. What is required is that target be successivelyincreased until the difference between it and MRCP is less than someminimum limit (which for all intents and purposes means that target andMRCP are equal). The difference between target and MRCP is compared tothe RCP limit, and a test is then performed to see if the limit isexceeded. If it is not, target has been sufficiently increased and abranch is taken to the bottom of FIG. 25 where the microprocessor is putto sleep and the system waits for the end of blanking. (It is to berecalled that all of this processing is taking place following thegeneration of a pacing pulse).

If the limit is exceeded, then target adjuster is increased. Referringto FIG. 18, for Case 2 the value stored in the minimum rate tweekregister is added to the adjuster register. The value stored in theminimum rate tweek register depends on the calibration speed, and it is16 times larger than the tweek factor. This is not to say that Rule 2results in the increase of target at a rate which is only 16 timesfaster than the rate at which target is increased or decreased in Cases1 and 3. That is because the only time that the tweek factor is added toor subtracted from the adjuster register is when there is an overflow orunderflow from the tweeker register. Thus target is increased in Case 2much faster than just 16 times relative to the speeds in Cases 1 and 3.

As shown on the flow chart of FIG. 24, after the minimum rate tweek isadded to the target adjuster register, a check is made to see whetherthere has been an overflow from the adjuster register. If there has notbeen an overflow, the microprocessor is put to sleep, awaiting the endof the blanking period. If there has been an overflow, then as shown onFIG. 18 the value of target is incremented. As shown on FIG. 25, aftertarget is incremented a check is made to see whether target has beenincremented out of range. If not, the system waits for the end ofblanking in the usual way. But if target has been incremented out ofrange, some additional processing is required.

The integrator which measures the RCP is provided with two possiblegains. Target basically follows the RCP measurements, so that one way todecrease target so that it gets back within range is to decrease thegain of the integrator. Therefore, a test is made to see if theintegrator is already set to have its low gain value. If it is, nothingcan be done to get target back into range. The RCP out-of-range flag isset to indicate that rate response is no longer possible, and thisinformation can be telemetered out to the programmer. Stat Set pacing(VVI, 70 ppm, 10 mA/1 ms) ensues, and the system awaits for the end ofblanking in the usual way. On the other hand, if the integrator is notalready set to have its low gain value, the gain value is now switched.Because this means that each RCP sample will be reduced in value, thepresent value of target also has to be reduced. At the bottom of FIG. 25there is a step which provides for setting target for the switch to lowgain, that is, reducing its value by the same factor by which the gainhas been reduced--thereby bringing it back in range. Processing thencontinues in the usual fashion, with rate response still enabled.

Returning to the bottom of FIG. 23, the right branch is taken if thenewly adjusted rate is somewhere between the minimum and maximum limits.Although the rate has been adjusted, it is still necessary to changetarget in accordance with either Rule 1 or Rule 3. The rate is aboveminimum rate, but it can be due to an intrinsic rhythm having made thepacer increase its rate in order to pace the heart so that an evokedpotential could be measured (Case 3), or the rate may be above theminimum rate due to the rate response (Case 1). An overdrive flag, to bedescribed below, is set when the pacing rate is increased, even thoughtnot called for by rate response, in order that a pacing pulse capturethe heart so that an evoked potential may be processed. At the top ofFIG. 24, the overdrive flag is examined. If it is set, representing Case3, the overdrive flag is now reset, and the rate is decreased 5 ppm. Theoverdrive flag is reset so that another decrease in rate will not occurduring a subsequent pass through the loop. The rate is decreased tocompensate for the increase (to be described below) which ensuredcapture. (No matter how many times the rate may have been increased by 5ppm in order that the pacing rate just exceed the intrinsic rate so thatan evoked potential could be processed, only a single decrease of 5 ppmtakes place; it is desirable to have the pacing rate just below theintrinsic rate.)

It will be recalled that when overdriving is necessary in order that apacing pulse be generated so that an evoked response can be processed,separate and apart from decreasing the pacing rate by 5 ppm to cancelthe overdrive, it is desirable to decrease the pacing rate by 5 ppm foronly the next cycle; as described above, this helps ensure that the nextintrinsic beat takes precedence over a paced beat. This is accomplishedby the step of FIG. 24 which indicates that the next cycle length isincreased by the equivalent of 5 ppm. (This terminology is used becauseit is not really the rate which is decreased since the decreased rate isapplicable for only one cycle; it is perhaps more proper to talk interms of increasing the cycle length.) The processing of target thencontinues. A test is performed to see if MRCP equals target. If it does,there is nothing further to do and a branch is taken to the bottom ofFIG. 25 where the microprocessor is put to sleep awaiting the end ofblanking. On the other hand, if the measured RCP is not equal to target,since what is being dealt with is Case 3, it is necessary to increasetarget, but at the slow rate of Case 1 rather than the fast rate of Case2. Referring to FIG. 18, what is required in this case is the additionof a value from the rate table, which is dependent on the present rate,to the tweeker register. This step is shown in FIG. 24. A test is thenmade to see if there is an overflow from the tweeker register. If not,the microprocessor is put to sleep in the usual way. If there is anoverflow, referring to FIG. 18 what is required is that the tweek factorbe added to the adjuster register, and this is what the flow chartshows. Thereafter, the overflow test is performed to see whether targetshould be incremented, and the processing takes the path describedabove.

The only other case to consider is that in which the overdrive flag isnot set, with a branch being taken to the right when theoverdrive-flag-set test is performed; this branch is taken when thepresent rate is above the minimum rate due to rate response. Rule 1requires that a value from the rate table be subtracted from the tweekerregister, and this is shown in FIG. 24. A test is now performed to seeif there is an underflow. If there is no underflow, the microprocessoris put to sleep and the system waits for an end to blanking. If there isan underflow, referring to FIG. 18 what is now required is that thetweek factor be subtracted from the adjuster register. This step isshown in the right path on FIG. 24. The test is then made to see ifthere is an underflow from the adjuster. If there is, target isdecremented.

When target was incremented in Cases 2 and 3, a test was performed tosee if target was out of range by reason of being too large. When targetis decremented in Case 1, a comparable test is performed to see if it isout of range, but this time by reason of being too small. If it is notout of range, processing resumes in the usual manner with the systemwaiting for the end of blanking. But if target is too small, the systemchecks whether the integrator is set at its high gain. If it is, thereis no way that the gain can be increased so as to increase target. TheRCP-out-of-range flag is set and Stat Set pacing takes over. But if theintegrator is presently at its low gain setting, the gain is switched tothe high value. At the same time, because all values of RCP will belarger, the present value of target must be increased for the newhigh-gain operation (which is what brings target back into range).Processing then continues in the usual manner.

The microprocessor awakens with timeout of the blanking timer.(Referring to the top of FIG. 21, the timeout may occur at that point inthe processing as previously described. But in either case, an entry ismade to the end blanking module on FIG. 26.) Blanking of the senseamplifier now ceases, and the rate time is set. The rate timer times theescape interval, in accordance with the current rate if it has beenadjusted by the rate response processing. If the blanking timer was setby the generation of a back-up pulse, then the escape interval is setnot from the generation of the back-up pulse, but rather from 60milliseconds earlier when the ordinary pacing stimulus was generated.The reason for this is that if the back-up pulse resulted from a fusionbeat, the back-up pulse did not accomplish any function, and in orderfor the next pacing stimulus to capture the heart it should be timedfrom the fusion beat.

A test is then performed to see whether it is time for a thresholdsearch. If it is not time, a branch is taken to the middle of FIG. 27where the microprocessor is put to sleep again, this time waiting for atimeout of the rate timer. As described above, a threshold search isperformed approximately once every twelve hours, or upon request by theprogrammer. If it is time for a threshold search, the first question iswhether the search has already been instituted. (An example of asearch-in-progress is represented by the setting of the search inprogress flag on FIG. 22.) If a search is not yet in progress, threesteps are executed. First, rate response is disabled because it is notoperative during the search. Second, the signature flag is set becauseit is necessary to issue a two-pulse signature so that anyone reviewingan ECG trace will understand what is going on. Third, the output is setto 1 milliampere and the programmed starting pulse width, as describedabove in connection with the description of the threshold search routinedepicted on FIG. 29. This is all that happens during the first passthrough the steps on FIG. 26.

The next time around, or even the first time if the search-in-progressflag was set during the processing on FIG. 22, the search-in-progressquestion is answered affirmatively. If there have been 25 beats of noiseor sensing since the threshold search began, the search is aborted, andthe output is returned to its previous value. But if the search isongoing, the system checks whether capture has been verified threetimes. The actual incrementing of the output during a threshold searchis performed on the left side of FIG. 22. The processing on FIGS. 26 and27 is concerned more with what happens as a result of the completion ofa threshold search or a regain of capture following a loss. In eitherevent, the system checks whether capture has been verified three timesin succession. As mentioned above, capture is verified three times toinsure that a reliable threshold has been determined and to reduce thepossibility of fusion beats causing a false indication of capturethreshold. If capture has been verified three times, a test is performedto see whether the threshold search in progress is one of the "alternatescheduled." A threshold search is performed approximately every twelvehours. The system records the final threshold value on alternatesearches so that it has available one threshold value for approximatelyeach day. The 32 most recent threshold values are stored in a32-location memory. It is of considerable aid to a physician to knowon-going changes in the threshold during the first 30 days or sofollowing implantation of a new lead. (The memory should have a minimumof 7 locations, for storing a week's worth of threshold values--at leastone value per day.) The information is made available by telemetering itout of the pacemaker to a programmer.

Continuing with the flow chart on FIG. 27, following the determinationof a new pulse energy value and its storage in memory, thesear-in-progress flag is reset; the search is over. The output is alsoincremented two steps as a safety margin. The signature flag is set sothat a pulse pair will serve to identify the completion of the thresholdsearch. The system then determines the RCP sample time as describedabove, following which rate response is enabled once again if it hasbeen programmed on. Thereafter, the pacemaker stops its processing andwaits for the rate timer timeout.

If the rate timer times out, it means that a pacing pulse is required.The processing continues at point A on FIG. 19. On the other hand, ifthere is no rate timer timeout, it is because an intrinsic beat has beensensed. As shown at the bottom of FIG. 27, the system remains in a looplooking for either a timeout or an intrinsic beat. If it is an intrinsicbeat which is the outcome, the "sensed" module on FIG. 2B is entered.

The first step in this module is to check whether what is believed tohave been the sensing of an intrinsic beat fell within the refractoryperiod. If it did, it is not treated as an intrinsic beat, and the loopat the bottom of FIG. 27 is re-entered so that the system can wait foreither another sensing or a rate timer timeout. But if the sensed beatwas outside the refractory interval, a test is made to see if the systemis programmed to operate in the VVT mode. If it is, it means that everysensing is to be followed by a pacing pulse and the processing resumesat the top of FIG. 18. The processing on the right side of FIG. 28 isbypassed; this processing has to do with rate response, and rateresponse as well as automatic output regulation can be enabled only whenthe pacer is set to operate in the VVI mode.

Assuming that the pacer is operating in the VVI mode, the telemetry coilis pulsed for the same reason that it is on FIG. 20; the best time forprogramming to commence is immediately after the generation of a pacingpulse (FIG. 20) or immediately after the sensing of an intrinsic beat(FIG. 28), thereby lessening the chance of any interference with pacingfunctions by the programming. A sense marker is then outputted since anintrinsic beat has been sensed.

The processing on the right side of FIG. 28 pertains to overdriving(increasing the rate above the intrinsic rate) so that an evokedpotential may be processed. The condition "overdrive enabled" means thatrate response has been programmed on (in which case capture must be hadso that an RCP measurement may be made), or--even if rate response hasbeen programmed off--a periodic threshold search is being performed.(Even in the absence of rate response, in order to conserve energy theoutput amplitude and pulse width should not be unnecessarily high.) Ifoverdrive is not enabled, it simply means that there is no reason toensure that a paced event takes place so that an evoked potential can bemeasured, and processing continues at the top of FIG. 26 with entry intothe end blanking module. Although the blanking timer has not been setand there is no blanking to stop, the processing does continue withsetting of the rate timer; since an intrinsic beat has been sensed, therate timer is set to time from this event.

If the overdrive enabled test is answered in the affirmative, it meansthat the rate should be increased to the point at which it just exceedsthe intrinsic rate so that a paced event can take place in order for anevoked potential to be processed. However, this should happen only whenit is appropriate. The first test which is now performed is to determinewhether a threshold search is in progress (FIG. 29) or targetinitialization is in progress (FIG. 30). In either case, it is desiredthat there be a paced event in every cycle and a jump is taken to checkwhether the pacing rate is already at the maximum rate. If it is, thereis no way in which it can be increased and a jump is made to the endblanking module on FIG. 26 where the rate timer is set. If neither athreshold search nor target initialization is in progress, a test ismade whether the present cycle is the fourth since the last time thatany evoked response measurement was made. If it is not, there is noreason to increase the pacing rate so that a paced event will occurinstead of an intrinsic beat, and the end blanking module is entered. Onthe other hand, if it is the fourth beat and an evoked response isdesired, since an intrinsic beat just took place overdrive is necessary.The maximum rate test is performed in this case as well as during athreshold search and target initialization.

If the present rate is not at the maximum, the rate is increased by 5ppm and the overdrive flag is set. It will be recalled that it is thesetting of the overdrive flag which controls the branching at the top ofFIG. 24; the state of the flag is an indication whether the currentrate, which is above the minimum, is due to overdriving or rateresponse. The rate is increased 5 ppm along with setting of theoverdrive flag in order that the next stimulus capture the heart; therate is decreased 5 ppm immediately following testing of the overdriveflag on FIG. 24 (which point is reached only if there has been a heartcapture) when it is determined that the flag is set and that the ratewas increased by at least 5 ppm in order to obtain a paced event. Aftersetting the overdrive flag and increasing the rate on FIG. 28, thesystem moves on to the top of FIG. 26 to the end blanking module. Itshould be borne in mind that there may have to be several 5-ppm rateincreases until capture is obtained, in which case the steps on FIG. 28may be executed during each of several successive cycles. Nevertheless,there is only one 5-ppm rate reduction on FIG. 24 because the pacingrate should end up just below the intrinsic rate, unless, of course, itis increased by rate response.

Although the invention has been described with reference to a particularembodiment, it is to be understood that this embodiment is merelyillustrative of the application of the principles of the invention.Numerous modifications may be made therein and other arrangements may bedevised without departing from the spirit and scope of the invention.

We claim:
 1. A pacemaker comprising means for generating pacing pulses;means for adjusting the magnitude of said pacing pulses; means forsensing an evoked potential following the generation of a pacing pulsein order to determine if an adjustment is required in the magnitude ofsaid pacing pulses; and means responsive to the failure to sense anevoked potential following the generation of a pacing pulse forincreasing the pacing rate so that if said failure was due to a fusionbeat, then the next pacing pulse is more likely to result in a heartcapture.
 2. A pacemaker in accordance with claim 1 wherein said rateincreasing means increases the pacing rate in both of two successiveheart cycles responsive to two successive failures to sense evokedpotentials.
 3. A pacemaker in accordance with claim 1 further includingmeans for controlling the generation of a back-up pacing pulseresponsive to the failure to sense an evoked potential.
 4. A pacemakerin accordance with claim 3 further including means responsive to thefailure to sense an evoked potential following generation of a back-uppacing pulse for determining that the preceding pacing pulse resulted ina fusion beat.
 5. A pacemaker in accordance with claim 4 wherein saiddetermining means is further operative, responsive to the sensing of anevoked potential following generation of a back-up pulse, fordetermining that the preceding pacing pulse resulted in a heart capturefailure.
 6. A pacemaker in accordance with claim 4 further includingmeans responsive to the sensing of an evoked potential followinggeneration of a back-up pulse for determining that the preceding pacingpulse resulted in a heart capture failure.
 7. A method of operating apacemaker comprising the steps of generating pacing pulses; adjustingthe magnitude of said pacing pulses; sensing an evoked potentialfollowing the generation of a pacing pulse in order to determine if anadjustment is required in the magnitude of said pacing pulses; andresponsive to the failure to sense an evoked potential following thegeneration of a pacing pulse, increasing the pacing rate so that if saidfailure was due to a fusion beat, then the next pacing pulse is morelikely to result in a heart capture.
 8. A method of operating apacemaker in accordance with claim 7 wherein said rate is increased inboth of two successive heart cycles responsive to two successivefailures to sense evoked potentials.
 9. A method of operating apacemaker in accordance with claim 7 further including the step ofcontrolling the generation of a back-up pacing pulse responsive to thefailure to sense an evoked potential.
 10. A method of operating apacemaker in accordance with claim 9 wherein, responsive to the failureto sense an evoked potential following generation of a back-up pacingpulse, it is determined that the preceding pacing pulse resulted in afusion beat.
 11. A method of operating a pacemaker in accordance withclaim 10 wherein, responsive to the sensing of an evoked potentialfollowing generation of a back-up pulse, it is determined that thepreceding pacing pulse resulted in a heart capture failure.